MutationT@ster 2025

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Input seems to be ok - now mapping the variant to the different transcripts...
Querying Taster for transcript #1: ENST00000258781
Querying Taster for transcript #2: ENST00000544363
Querying Taster for transcript #3: ENST00000541586
MT speed 0.44 s - this script 3.043449 s

Transcript summary:

Permalink

Transcript	Gene symbol	Prediction	Tree vote	Model	Splice site change	Known ClinVar disease mutation	Amino acid changes	Variant type	Protein length	Features at a glance
ENST00000544363	CCM2	Deleterious	9\|1	complex_aae	No	Yes	E4*	Single base exchange	Delayed start of translation	Amino acid sequence changed Frameshift Known disease mutation: ClinVar ID 2684 (pathogenic) Kozak consensus sequence changed Protein features (might be) affected Start ATG shifted
ENST00000258781(MANE Select)	CCM2	Deleterious	9\|1	complex_aae	No	Yes	E4*	Single base exchange	Delayed start of translation	Amino acid sequence changed Frameshift Known disease mutation: ClinVar ID 2684 (pathogenic) Kozak consensus sequence changed Protein features (might be) affected Start ATG shifted
ENST00000541586	CCM2	Deleterious	10\|0	complex_aae	No	Yes	L12*	Single base exchange	Delayed start of translation	Amino acid sequence changed Frameshift Known disease mutation: ClinVar ID 2684 (pathogenic) Kozak consensus sequence changed Protein features (might be) affected Start ATG shifted

MutationT@ster 2025

Variant:

7:45000334A>G_2_ENST00000544363

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Frameshift
Known disease mutation: ClinVar ID 2684 (pathogenic)
Kozak consensus sequence changed
Protein features (might be) affected
Start ATG shifted

Model: complex_aae
Tree vote: 9|1 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr7:45000334A>G (GRCh38)

Gene symbol

CCM2

Gene constraints

LOEUF: 0.86, LOF (oe): 0.58, misssense (oe): 0.79, synonymous (oe): 0.88 ? (gnomAD)

Ensembl transcript ID

ENST00000544363.5

Genbank transcript ID

NM_001167935 (by similarity)

UniProt / AlphaMissense peptide

CCM2_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS
spans start ATG

DNA changes

c.1A>G
g.860A>G

AA changes

M1? initiating Methionine lost
possible effect: activation of potential downstream translation initiation site with new reading frame

AAE:	E2R	E3R	E4*	G5-	K6-	K7-	G8-	K9-	K10-	P11-	G12-	I13-	V14-	S15-	P16-	F17-	K18-	R19-	V20-	F21-	L22-	K23-	G24-	E25-	K26-	S27-	R28-	D29-	K30-	K31-	A32-	H33-	E34-	K35-	V36-	T37-	E38-	R39-	R40-	P41-	L42-	H43-	T44-	V45-	V46-	L47-	S48-	L49-	P50-	E51-	R52-	V53-	E54-	P55-	D56-	R57-	L58-	L59-	S60-	D61-	Y62-	I63-	E64-	K65-	E66-	V67-	K68-	Y69-	L70-	G71-	Q72-	L73-	T74-	S75-	I76-	P77-	G78-	Y79-	L80-	N81-	P82-	S83-	S84-	R85-	T86-	E87-	I88-	L89-	H90-	F91-	I92-	D93-	N94-	A95-	K96-	R97-	A98-	H99-	Q100-	L101-	P102-	G103-	H104-	L105-	T106-	Q107-	E108-	H109-	D110-	A111-	V112-	L113-	S114-	L115-	S116-	A117-	Y118-	N119-	V120-	K121-	L122-	A123-	W124-	R125-	D126-	G127-	E128-	D129-	I130-	I131-	L132-	R133-	V134-	P135-	I136-	H137-	D138-	I139-	A140-	A141-	V142-	S143-	Y144-	V145-	R146-	D147-	D148-	A149-	A150-	H151-	L152-	V153-	V154-	L155-	K156-	T157-	D158-	D159-	S160-	S161-	T162-	K163-	V164-	D165-	I166-	K167-	E168-	T169-	Y170-	E171-	V172-	E173-	A174-	S175-	T176-	F177-	C178-	F179-	P180-	E181-	S182-	V183-	D184-	V185-	G186-	G187-	A188-	S189-	P190-	H191-	S192-	K193-	T194-	I195-	S196-	E197-	S198-	E199-	L200-	S201-	A202-	S203-	A204-	T205-	E206-	L207-	L208-	Q209-	D210-	Y211-	M212-	L213-	T214-	L215-	R216-	T217-	K218-	L219-	S220-	S221-	Q222-	E223-	I224-	Q225-	Q226-	F227-	A228-	A229-	L230-	L231-	H232-	E233-	Y234-	R235-	N236-	G237-	A238-	S239-	I240-	H241-	E242-	F243-	C244-	I245-	N246-	L247-	R248-	Q249-	L250-	Y251-	G252-	D253-	S254-	R255-	K256-	F257-	L258-	L259-	L260-	G261-	L262-	R263-	P264-	F265-	I266-	P267-	E268-	K269-	D270-	S271-	Q272-	H273-	F274-	E275-	N276-	F277-	L278-	E279-	T280-	I281-	G282-	V283-	K284-	D285-	G286-	R287-	G288-	I289-	I290-	T291-	D292-	S293-	F294-	G295-	R296-	H297-	R298-	R299-	A300-	L301-	S302-	T303-	T304-	S305-	S306-	S307-	T308-	T309-	N310-	G311-	N312-	R313-	A314-	T315-	G316-	S317-	S318-	D319-	D320-	R321-	S322-	A323-	P324-	S325-	E326-	G327-	D328-	E329-	W330-	D331-	R332-	M333-	I334-	S335-	D336-	I337-	S338-	S339-	D340-	I341-	E342-	A343-	L344-	G345-	C346-	S347-	M348-	D349-	Q350-	D351-	S352-	A353-	*354-	?
Score:	54	54	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

Frameshift

Yes

Length of protein

Delayed start of translation

Pathogenic variant (ClinVar)

Cerebral cavernous malformation 2

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs137852842
gnomAD	homozygous (G/G)	heterozygous	allele carriers
	0	3	3

Protein conservation

Species	Match	AA
Human		2	M	E	E	E	G	K	K	G	K	K	P	G	I	V
mutated	no alignment	n/a
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
1	37	REGION		lost
1	444	CHAIN		lost
15	15	MOD_RES	Phosphoserine	lost
21	37	COMPBIAS	Basic and acidic residues	lost
57	60	TURN		lost
59	248	DOMAIN	PID	lost
63	76	STRAND		lost
85	97	HELIX		lost
110	115	STRAND		lost
117	127	STRAND		lost
130	135	STRAND		lost
136	138	HELIX		lost
139	146	STRAND		lost
151	157	STRAND		lost
164	164	MOD_RES	Phosphoserine	lost
193	202	STRAND		lost
203	219	HELIX		lost
225	238	HELIX		lost
283	376	REGION		lost
288	291	HELIX		lost
293	306	HELIX		lost
307	309	TURN		lost
312	326	HELIX		lost
331	342	HELIX		lost
344	356	HELIX		lost
359	371	HELIX		lost
373	375	TURN		lost
384	384	MOD_RES	Phosphoserine	lost
391	412	COMPBIAS	Polar residues	lost
391	423	REGION		lost
393	393	MOD_RES	Phosphoserine	lost
394	394	MOD_RES	Phosphothreonine	lost
396	396	MOD_RES	Phosphoserine	lost
399	399	MOD_RES	Phosphothreonine	lost
422	435	HELIX		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.147	0.036
	0.436	0.172
(flanking)	0.279	0.465

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

7

Strand

1

Original gDNA sequence snippet

CGGGAGCCGCACGCGGCGATATGGAAGAGGAGGGCAAGAAG

Altered gDNA sequence snippet

CGGGAGCCGCACGCGGCGATGTGGAAGAGGAGGGCAAGAAG

Original cDNA sequence snippet

CGGGAGCCGCACGCGGCGATATGGAAGAGGAGGGCAAGAAG

Altered cDNA sequence snippet

CGGGAGCCGCACGCGGCGATGTGGAAGAGGAGGGCAAGAAG

Wildtype AA sequence

MEEEGKKGKK PGIVSPFKRV FLKGEKSRDK KAHEKVTERR PLHTVVLSLP ERVEPDRLLS
DYIEKEVKYL GQLTSIPGYL NPSSRTEILH FIDNAKRAHQ LPGHLTQEHD AVLSLSAYNV
KLAWRDGEDI ILRVPIHDIA AVSYVRDDAA HLVVLKTDDS STKVDIKETY EVEASTFCFP
ESVDVGGASP HSKTISESEL SASATELLQD YMLTLRTKLS SQEIQQFAAL LHEYRNGASI
HEFCINLRQL YGDSRKFLLL GLRPFIPEKD SQHFENFLET IGVKDGRGII TDSFGRHRRA
LSTTSSSTTN GNRATGSSDD RSAPSEGDEW DRMISDISSD IEALGCSMDQ DSA*

Mutated AA sequence

MRR*

Position of stopcodon in wt / mu CDS

1062 / 12

Position (AA) of stopcodon in wt / mu AA sequence

354 / 4

Position of stopcodon in wt / mu cDNA

1208 / 158

Position of start ATG in wt / mu cDNA

147 / 244

Last intron/exon boundary

927

Theoretical NMD boundary in CDS

730

Length of CDS

1062

Coding sequence (CDS) position

1

cDNA position

147

gDNA position

860

Chromosomal position

45000334

Speed

0.13 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

Back to summary table

MutationT@ster 2025

Variant:

7:45000334A>G_1_ENST00000258781

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Frameshift
Known disease mutation: ClinVar ID 2684 (pathogenic)
Kozak consensus sequence changed
Protein features (might be) affected
Start ATG shifted

Model: complex_aae
Tree vote: 9|1 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr7:45000334A>G (GRCh38)

Gene symbol

CCM2

Gene constraints

LOEUF: 0.75, LOF (oe): 0.53, misssense (oe): 0.80, synonymous (oe): 0.87 ? (gnomAD)

Ensembl transcript ID

ENST00000258781.11

Genbank transcript ID

NM_031443 (exact from MANE), NM_001363458 (by similarity)

UniProt / AlphaMissense peptide

CCM2_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS
spans start ATG

DNA changes

c.1A>G
g.860A>G

AA changes

M1? initiating Methionine lost
possible effect: activation of potential downstream translation initiation site with new reading frame

AAE:	E2R	E3R	E4*	G5-	K6-	K7-	G8-	K9-	K10-	P11-	G12-	I13-	V14-	S15-	P16-	F17-	K18-	R19-	V20-	F21-	L22-	K23-	G24-	E25-	K26-	S27-	R28-	D29-	K30-	K31-	A32-	H33-	E34-	K35-	V36-	T37-	E38-	R39-	R40-	P41-	L42-	H43-	T44-	V45-	V46-	L47-	S48-	L49-	P50-	E51-	R52-	V53-	E54-	P55-	D56-	R57-	L58-	L59-	S60-	D61-	Y62-	I63-	E64-	K65-	E66-	V67-	K68-	Y69-	L70-	G71-	Q72-	L73-	T74-	S75-	I76-	P77-	G78-	Y79-	L80-	N81-	P82-	S83-	S84-	R85-	T86-	E87-	I88-	L89-	H90-	F91-	I92-	D93-	N94-	A95-	K96-	R97-	A98-	H99-	Q100-	L101-	P102-	G103-	H104-	L105-	T106-	Q107-	E108-	H109-	D110-	A111-	V112-	L113-	S114-	L115-	S116-	A117-	Y118-	N119-	V120-	K121-	L122-	A123-	W124-	R125-	D126-	G127-	E128-	D129-	I130-	I131-	L132-	R133-	V134-	P135-	I136-	H137-	D138-	I139-	A140-	A141-	V142-	S143-	Y144-	V145-	R146-	D147-	D148-	A149-	A150-	H151-	L152-	V153-	V154-	L155-	K156-	T157-	A158-	Q159-	D160-	P161-	G162-	I163-	S164-	P165-	S166-	Q167-	S168-	L169-	C170-	A171-	E172-	S173-	S174-	R175-	G176-	L177-	S178-	A179-	G180-	S181-	L182-	S183-	E184-	S185-	A186-	V187-	G188-	P189-	V190-	E191-	A192-	C193-	C194-	L195-	V196-	I197-	L198-	A199-	A200-	E201-	S202-	K203-	V204-	A205-	A206-	E207-	E208-	L209-	C210-	C211-	L212-	L213-	G214-	Q215-	V216-	F217-	Q218-	V219-	V220-	Y221-	T222-	E223-	S224-	T225-	I226-	D227-	F228-	L229-	D230-	R231-	A232-	I233-	F234-	D235-	G236-	A237-	S238-	T239-	P240-	T241-	H242-	H243-	L244-	S245-	L246-	H247-	S248-	D249-	D250-	S251-	S252-	T253-	K254-	V255-	D256-	I257-	K258-	E259-	T260-	Y261-	E262-	V263-	E264-	A265-	S266-	T267-	F268-	C269-	F270-	P271-	E272-	S273-	V274-	D275-	V276-	G277-	G278-	A279-	S280-	P281-	H282-	S283-	K284-	T285-	I286-	S287-	E288-	S289-	E290-	L291-	S292-	A293-	S294-	A295-	T296-	E297-	L298-	L299-	Q300-	D301-	Y302-	M303-	L304-	T305-	L306-	R307-	T308-	K309-	L310-	S311-	S312-	Q313-	E314-	I315-	Q316-	Q317-	F318-	A319-	A320-	L321-	L322-	H323-	E324-	Y325-	R326-	N327-	G328-	A329-	S330-	I331-	H332-	E333-	F334-	C335-	I336-	N337-	L338-	R339-	Q340-	L341-	Y342-	G343-	D344-	S345-	R346-	K347-	F348-	L349-	L350-	L351-	G352-	L353-	R354-	P355-	F356-	I357-	P358-	E359-	K360-	D361-	S362-	Q363-	H364-	F365-	E366-	N367-	F368-	L369-	E370-	T371-	I372-	G373-	V374-	K375-	D376-	G377-	R378-	G379-	I380-	I381-	T382-	D383-	S384-	F385-	G386-	R387-	H388-	R389-	R390-	A391-	L392-	S393-	T394-	T395-	S396-	S397-	S398-	T399-	T400-	N401-	G402-	N403-	R404-	A405-	T406-	G407-	S408-	S409-	D410-	D411-	R412-	S413-	A414-	P415-	S416-	E417-	G418-	D419-	E420-	W421-	D422-	R423-	M424-	I425-	S426-	D427-	I428-	S429-	S430-	D431-	I432-	E433-	A434-	L435-	G436-	C437-	S438-	M439-	D440-	Q441-	D442-	S443-	A444-	*445-	?
Score:	54	54	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

Frameshift

Yes

Length of protein

Delayed start of translation

Pathogenic variant (ClinVar)

Cerebral cavernous malformation 2

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs137852842
gnomAD	homozygous (G/G)	heterozygous	allele carriers
	0	3	3

Protein conservation

Species	Match	AA
Human		2	M	E	E	E	G	K	K	G	K	K	P	G	I	V	S	P	F	K	R	V	F	L	K	G	E	K	S	R	D	K	K	A	H	E	K	V	T	E	R	R	P	L	H	T	V	V	L	S	L	P	E	R	V	E	P	D	R	L	L	S	D	Y	I	E	K	E	V	K	Y	L	G	Q	L	T	S	I	P	G	Y	L	N	P	S	S	R	T	E	I	L	H	F	I	D	N	A	K	R	A	H	Q	L	P	G	H	L	T	Q	E	H	D	A	V	L	S	L	S	A	Y	N	V	K	L	A	W	R	D	G	E	D	I	I	L
mutated	no alignment	n/a
Ptroglodytes	no alignment	n/a
Mmulatta	all identical	2	M	E	E	E	G	K	K	G	K	K	P	G	I	V	S	P	F	K	R	V	F	L	K	G	E	K	S	R	D	K	K	A	H	E	K	V	T	E	R	R	P	L	H	T	V	V	L	S	L	P	E	R	V	E	P	D	R	L	L	S	D	Y	I	E	K	E	V	K	Y	L	G	Q	L	T	S	I	P	G	Y	L	N	P	S	S	R	T	E	I	L	H	F	I	D	N	A	K	R	A	H	Q	L	P	G	H	L	T	Q	E	H	D	A	V	L	S	L	S	A	Y	N	V
Fcatus	partly conserved	2	M	D	E	E	G	K	K	G	K	K	P	G	I	V	S	P	F	K	R	V	F	L	K	G	E	K	S	R	D	K	K	A	H	E	K	V	T	E	R	R	P	L	H	T	V	A	L	S	L	P	E	R	V	E	P	D	R	L	L	S	D	Y	I	E	K	E	V	K	Y	L	G	Q	L	T	S	I	P	G	Y	L	N	P	S	S	R	T	E	I	L	H	F	I	D	N	A	K	R	A	H	Q	L	P	G	H	L	T	Q	E	H	D	A	V	I	S	L	S	A	Y	N	V
Mmusculus	partly conserved	2	M	E	E	E	G	K	K	G	K	K	P	G	I	V	S	P	F	K	R	V	F	L	K	G	E	K	S	R	D	K	K	A	H	E	K	V	T	E	R	R	P	L	H	T	V	V	L	A	L	P	E	R	V	E	P	D	R	L	L	S	D	Y	I	E	K	E	V	K	Y	L	G	Q	L	T	S	I	P	G	Y	L	N	P	S	S	R	T	E	I	L	H	F	I	D	K	A	K	R	S	H	Q	L	P	G	H	L	T	Q	E	H	D	A	V	L	S	L	S	A	Y	N	V
Ggallus	no alignment	n/a
Trubripes	partly conserved	2	M	E	E	D	V	K	K	V	K	K	P	G	I	V	S	P	F	K	R	V	F	L	K	G	E	K	G	R	D	K	K	A	Q	E	K	T	T	E	R	R	A	L	H	T	F	S	L	S	Q	P	D	HH	I	D	P	D	I	L	L	N	D	Y	I	E	K	E	V	K	Y	L	G	Q	L	T	S	V	P	G	Y	L	N	P	S	S	R	T	E	M	L	Q	L	I	D	T	A	R	K	S	H	Q	L	A	G	Q	L	T	S	E	Q	D	A	V	V	S	L	S	A	Y	N
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no alignment	n/a

Protein features

Start (aa)	End (aa)	Feature	Details
1	37	REGION		lost
1	444	CHAIN		lost
15	15	MOD_RES	Phosphoserine	lost
21	37	COMPBIAS	Basic and acidic residues	lost
57	60	TURN		lost
59	248	DOMAIN	PID	lost
63	76	STRAND		lost
85	97	HELIX		lost
110	115	STRAND		lost
117	127	STRAND		lost
130	135	STRAND		lost
136	138	HELIX		lost
139	146	STRAND		lost
151	157	STRAND		lost
164	164	MOD_RES	Phosphoserine	lost
193	202	STRAND		lost
203	219	HELIX		lost
225	238	HELIX		lost
283	376	REGION		lost
288	291	HELIX		lost
293	306	HELIX		lost
307	309	TURN		lost
312	326	HELIX		lost
331	342	HELIX		lost
344	356	HELIX		lost
359	371	HELIX		lost
373	375	TURN		lost
384	384	MOD_RES	Phosphoserine	lost
391	412	COMPBIAS	Polar residues	lost
391	423	REGION		lost
393	393	MOD_RES	Phosphoserine	lost
394	394	MOD_RES	Phosphothreonine	lost
396	396	MOD_RES	Phosphoserine	lost
399	399	MOD_RES	Phosphothreonine	lost
422	435	HELIX		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.147	0.036
	0.436	0.172
(flanking)	0.279	0.465

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

7

Strand

1

Original gDNA sequence snippet

CGGGAGCCGCACGCGGCGATATGGAAGAGGAGGGCAAGAAG

Altered gDNA sequence snippet

CGGGAGCCGCACGCGGCGATGTGGAAGAGGAGGGCAAGAAG

Original cDNA sequence snippet

CGGGAGCCGCACGCGGCGATATGGAAGAGGAGGGCAAGAAG

Altered cDNA sequence snippet

CGGGAGCCGCACGCGGCGATGTGGAAGAGGAGGGCAAGAAG

Wildtype AA sequence

MEEEGKKGKK PGIVSPFKRV FLKGEKSRDK KAHEKVTERR PLHTVVLSLP ERVEPDRLLS
DYIEKEVKYL GQLTSIPGYL NPSSRTEILH FIDNAKRAHQ LPGHLTQEHD AVLSLSAYNV
KLAWRDGEDI ILRVPIHDIA AVSYVRDDAA HLVVLKTAQD PGISPSQSLC AESSRGLSAG
SLSESAVGPV EACCLVILAA ESKVAAEELC CLLGQVFQVV YTESTIDFLD RAIFDGASTP
THHLSLHSDD SSTKVDIKET YEVEASTFCF PESVDVGGAS PHSKTISESE LSASATELLQ
DYMLTLRTKL SSQEIQQFAA LLHEYRNGAS IHEFCINLRQ LYGDSRKFLL LGLRPFIPEK
DSQHFENFLE TIGVKDGRGI ITDSFGRHRR ALSTTSSSTT NGNRATGSSD DRSAPSEGDE
WDRMISDISS DIEALGCSMD QDSA*

Mutated AA sequence

MRR*

Position of stopcodon in wt / mu CDS

1335 / 12

Position (AA) of stopcodon in wt / mu AA sequence

445 / 4

Position of stopcodon in wt / mu cDNA

1468 / 145

Position of start ATG in wt / mu cDNA

134 / 231

Last intron/exon boundary

1187

Theoretical NMD boundary in CDS

1003

Length of CDS

1335

Coding sequence (CDS) position

1

cDNA position

134

gDNA position

860

Chromosomal position

45000334

Speed

0.17 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

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MutationT@ster 2025

Variant:

7:45000334A>G_3_ENST00000541586

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Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Frameshift
Known disease mutation: ClinVar ID 2684 (pathogenic)
Kozak consensus sequence changed
Protein features (might be) affected
Start ATG shifted

Model: complex_aae
Tree vote: 10|0 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr7:45000334A>G (GRCh38)

Gene symbol

CCM2

Gene constraints

LOEUF: 0.73, LOF (oe): 0.48, misssense (oe): 0.82, synonymous (oe): 0.89 ? (gnomAD)

Ensembl transcript ID

ENST00000541586.5

Genbank transcript ID

NM_001363459 (by similarity), NM_001167934 (by similarity)

UniProt / AlphaMissense peptide

CCM2_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS
spans start ATG

DNA changes

c.1A>G
g.860A>G

AA changes

M1? initiating Methionine lost
possible effect: activation of potential downstream translation initiation site with new reading frame

AAE:	E2Q	E3R	G5P	K6T	K7S	G8F	K9R	K10D	Y11T	L12*	G13-	Q14-	L15-	T16-	S17-	I18-	P19-	G20-	Y21-	L22-	N23-	P24-	S25-	S26-	R27-	T28-	E29-	I30-	L31-	H32-	F33-	I34-	D35-	N36-	A37-	K38-	R39-	A40-	H41-	Q42-	L43-	P44-	G45-	H46-	L47-	T48-	Q49-	E50-	H51-	D52-	A53-	V54-	L55-	S56-	L57-	S58-	A59-	Y60-	N61-	V62-	K63-	L64-	A65-	W66-	R67-	D68-	G69-	E70-	D71-	I72-	I73-	L74-	R75-	V76-	P77-	I78-	H79-	D80-	I81-	A82-	A83-	V84-	S85-	Y86-	V87-	R88-	D89-	D90-	A91-	A92-	H93-	L94-	V95-	V96-	L97-	K98-	T99-	A100-	Q101-	D102-	P103-	G104-	I105-	S106-	P107-	S108-	Q109-	S110-	L111-	C112-	A113-	E114-	S115-	S116-	R117-	G118-	L119-	S120-	A121-	G122-	S123-	L124-	S125-	E126-	S127-	A128-	V129-	G130-	P131-	V132-	E133-	A134-	C135-	C136-	L137-	V138-	I139-	L140-	A141-	A142-	E143-	S144-	K145-	V146-	A147-	A148-	E149-	E150-	L151-	C152-	C153-	L154-	L155-	G156-	Q157-	V158-	F159-	Q160-	V161-	V162-	Y163-	T164-	E165-	S166-	T167-	I168-	D169-	F170-	L171-	D172-	R173-	A174-	I175-	F176-	D177-	G178-	A179-	S180-	T181-	P182-	T183-	H184-	H185-	L186-	S187-	L188-	H189-	S190-	D191-	D192-	S193-	S194-	T195-	K196-	V197-	D198-	I199-	K200-	E201-	T202-	Y203-	E204-	V205-	E206-	A207-	S208-	T209-	F210-	C211-	F212-	P213-	E214-	S215-	V216-	D217-	V218-	G219-	G220-	A221-	S222-	P223-	H224-	S225-	K226-	T227-	I228-	S229-	E230-	S231-	E232-	L233-	S234-	A235-	S236-	A237-	T238-	E239-	L240-	L241-	Q242-	D243-	Y244-	M245-	L246-	T247-	L248-	R249-	T250-	K251-	L252-	S253-	S254-	Q255-	E256-	I257-	Q258-	Q259-	F260-	A261-	A262-	L263-	L264-	H265-	E266-	Y267-	R268-	N269-	G270-	A271-	S272-	I273-	H274-	E275-	F276-	C277-	I278-	N279-	L280-	R281-	Q282-	L283-	Y284-	G285-	D286-	S287-	R288-	K289-	F290-	L291-	L292-	L293-	G294-	L295-	R296-	P297-	F298-	I299-	P300-	E301-	K302-	D303-	S304-	Q305-	H306-	F307-	E308-	N309-	F310-	L311-	E312-	T313-	I314-	G315-	V316-	K317-	D318-	G319-	R320-	G321-	I322-	I323-	T324-	D325-	S326-	F327-	G328-	R329-	H330-	R331-	R332-	A333-	L334-	S335-	T336-	T337-	S338-	S339-	S340-	T341-	T342-	N343-	G344-	N345-	R346-	A347-	T348-	G349-	S350-	S351-	D352-	D353-	R354-	S355-	A356-	P357-	S358-	E359-	G360-	D361-	E362-	W363-	D364-	R365-	M366-	I367-	S368-	D369-	I370-	S371-	S372-	D373-	I374-	E375-	A376-	L377-	G378-	C379-	S380-	M381-	D382-	Q383-	D384-	S385-	A386-	*387-	?
Score:	29	54	42	78	121	153	26	101	92	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

Frameshift

Yes

Length of protein

Delayed start of translation

Pathogenic variant (ClinVar)

Cerebral cavernous malformation 2

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs137852842
gnomAD	homozygous (G/G)	heterozygous	allele carriers
	0	3	3

Protein conservation

Species	Match	AA
Human		2	M	E	E	E	G	K	K	G	K	K	Y	L	G	Q
mutated	no alignment	n/a
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
1	37	REGION		lost
1	444	CHAIN		lost
15	15	MOD_RES	Phosphoserine	lost
21	37	COMPBIAS	Basic and acidic residues	lost
57	60	TURN		lost
59	248	DOMAIN	PID	lost
63	76	STRAND		lost
85	97	HELIX		lost
110	115	STRAND		lost
117	127	STRAND		lost
130	135	STRAND		lost
136	138	HELIX		lost
139	146	STRAND		lost
151	157	STRAND		lost
164	164	MOD_RES	Phosphoserine	lost
193	202	STRAND		lost
203	219	HELIX		lost
225	238	HELIX		lost
283	376	REGION		lost
288	291	HELIX		lost
293	306	HELIX		lost
307	309	TURN		lost
312	326	HELIX		lost
331	342	HELIX		lost
344	356	HELIX		lost
359	371	HELIX		lost
373	375	TURN		lost
384	384	MOD_RES	Phosphoserine	lost
391	412	COMPBIAS	Polar residues	lost
391	423	REGION		lost
393	393	MOD_RES	Phosphoserine	lost
394	394	MOD_RES	Phosphothreonine	lost
396	396	MOD_RES	Phosphoserine	lost
399	399	MOD_RES	Phosphothreonine	lost
422	435	HELIX		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	0.147	0.036
	0.436	0.172
(flanking)	0.279	0.465

?

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

7

Strand

1

Original gDNA sequence snippet

CGGGAGCCGCACGCGGCGATATGGAAGAGGAGGGCAAGAAG

Altered gDNA sequence snippet

CGGGAGCCGCACGCGGCGATGTGGAAGAGGAGGGCAAGAAG

Original cDNA sequence snippet

CGGGAGCCGCACGCGGCGATATGGAAGAGGAGGGCAAGAAG

Altered cDNA sequence snippet

CGGGAGCCGCACGCGGCGATGTGGAAGAGGAGGGCAAGAAG

Wildtype AA sequence

MEEEGKKGKK YLGQLTSIPG YLNPSSRTEI LHFIDNAKRA HQLPGHLTQE HDAVLSLSAY
NVKLAWRDGE DIILRVPIHD IAAVSYVRDD AAHLVVLKTA QDPGISPSQS LCAESSRGLS
AGSLSESAVG PVEACCLVIL AAESKVAAEE LCCLLGQVFQ VVYTESTIDF LDRAIFDGAS
TPTHHLSLHS DDSSTKVDIK ETYEVEASTF CFPESVDVGG ASPHSKTISE SELSASATEL
LQDYMLTLRT KLSSQEIQQF AALLHEYRNG ASIHEFCINL RQLYGDSRKF LLLGLRPFIP
EKDSQHFENF LETIGVKDGR GIITDSFGRH RRALSTTSSS TTNGNRATGS SDDRSAPSEG
DEWDRMISDI SSDIEALGCS MDQDSA*

Mutated AA sequence

MQREPTSFRD T*

Position of stopcodon in wt / mu CDS

1161 / 36

Position (AA) of stopcodon in wt / mu AA sequence

387 / 12

Position of stopcodon in wt / mu cDNA

1307 / 182

Position of start ATG in wt / mu cDNA

147 / 253

Last intron/exon boundary

1026

Theoretical NMD boundary in CDS

829

Length of CDS

1161

Coding sequence (CDS) position

1

cDNA position

147

gDNA position

860

Chromosomal position

45000334

Speed

0.14 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

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