Mutagenetix > Incidental Mutation

Incidental Mutation 'R6954:Ccm2'

541380

Institutional Source

Beutler Lab

Gene Symbol

Ccm2

Ensembl Gene

ENSMUSG00000000378

Gene Name

cerebral cavernous malformation 2

Synonyms

MMRRC Submission

045066-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6954 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

6496887-6546744 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 6544239 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 345 (I345N)

Ref Sequence

ENSEMBL: ENSMUSP00000000388 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000000388] [ENSMUST00000045713] [ENSMUST00000109721] [ENSMUST00000109722] [ENSMUST00000159007] [ENSMUST00000160633] [ENSMUST00000161501]

AlphaFold

Q8K2Y9

Predicted Effect

probably damaging
Transcript: ENSMUST00000000388
AA Change: I345N

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: I345N

Domain	Start	End	E-Value	Type
low complexity region	2	12	N/A	INTRINSIC
Blast:PTB	60	230	2e-35	BLAST
low complexity region	242	252	N/A	INTRINSIC
Pfam:CCM2_C	296	396	8.9e-50	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000045713

SMART Domains

Protein: ENSMUSP00000049490
Gene: ENSMUSG00000041073

Domain	Start	End	E-Value	Type
low complexity region	2	28	N/A	INTRINSIC
low complexity region	70	87	N/A	INTRINSIC
low complexity region	228	235	N/A	INTRINSIC
low complexity region	266	277	N/A	INTRINSIC
low complexity region	294	306	N/A	INTRINSIC
low complexity region	328	354	N/A	INTRINSIC
low complexity region	391	422	N/A	INTRINSIC
low complexity region	454	479	N/A	INTRINSIC
internal_repeat_1	537	689	6.19e-8	PROSPERO
low complexity region	692	713	N/A	INTRINSIC
internal_repeat_1	732	889	6.19e-8	PROSPERO
low complexity region	924	939	N/A	INTRINSIC
low complexity region	1159	1170	N/A	INTRINSIC
low complexity region	1308	1325	N/A	INTRINSIC
Pfam:NAC	1357	1413	2.9e-24	PFAM
low complexity region	1449	1466	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000109721
AA Change: I281N

PolyPhen 2 Score 0.689 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378
AA Change: I281N

Domain	Start	End	E-Value	Type
Blast:PTB	2	166	2e-32	BLAST
low complexity region	178	188	N/A	INTRINSIC
low complexity region	230	244	N/A	INTRINSIC
PDB:4FQN\|D	245	324	5e-52	PDB

Predicted Effect

possibly damaging
Transcript: ENSMUST00000109722
AA Change: I281N

PolyPhen 2 Score 0.689 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378
AA Change: I281N

Domain	Start	End	E-Value	Type
Blast:PTB	2	166	2e-32	BLAST
low complexity region	178	188	N/A	INTRINSIC
low complexity region	230	244	N/A	INTRINSIC
PDB:4FQN\|D	245	324	5e-52	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000159007

SMART Domains

Protein: ENSMUSP00000125608
Gene: ENSMUSG00000000378

Domain	Start	End	E-Value	Type
low complexity region	2	10	N/A	INTRINSIC
Blast:PTB	11	102	3e-20	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000160633

SMART Domains

Protein: ENSMUSP00000125072
Gene: ENSMUSG00000000378

Domain	Start	End	E-Value	Type
Blast:PTB	54	224	6e-38	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000161501

SMART Domains

Protein: ENSMUSP00000123790
Gene: ENSMUSG00000000378

Domain	Start	End	E-Value	Type
Blast:PTB	40	122	3e-10	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000177050

Predicted Effect

probably benign
Transcript: ENSMUST00000177391

Meta Mutation Damage Score

0.0683

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.3%
20x: 97.5%

Validation Efficiency

98% (57/58)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions, and lumen formation in endothelial cells. Mutations in this gene result in cerebral cavernous malformations. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]
PHENOTYPE: Homozygous null mice die during embryonic development with vasculature defects in the heart and placenta. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 58 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930451I11Rik	A	T	7: 126,429,809 (GRCm39)		probably null	Het
Alox5	A	C	6: 116,397,241 (GRCm39)	Y314*	probably null	Het
Ap4e1	T	C	2: 126,906,871 (GRCm39)	S1044P	probably benign	Het
Ash2l	A	G	8: 26,312,796 (GRCm39)	V391A	possibly damaging	Het
B4galnt4	A	G	7: 140,647,145 (GRCm39)	T326A	probably benign	Het
Cntnap3	G	A	13: 64,896,373 (GRCm39)	H1034Y	probably benign	Het
Cpsf1	A	G	15: 76,483,696 (GRCm39)	L849S	probably damaging	Het
Ctrb1	A	G	8: 112,413,296 (GRCm39)	S239P	probably damaging	Het
Dennd1b	T	A	1: 139,096,683 (GRCm39)		probably benign	Het
Dnah17	A	G	11: 117,957,258 (GRCm39)	I2773T	probably damaging	Het
Eif2b2	T	A	12: 85,272,817 (GRCm39)	F267L	probably damaging	Het
Fcrl2	A	G	3: 87,170,983 (GRCm39)		probably benign	Het
Furin	G	T	7: 80,046,712 (GRCm39)	D181E	possibly damaging	Het
Gm29106	T	A	1: 118,128,317 (GRCm39)	C670S	probably damaging	Het
Gm6309	A	T	5: 146,105,300 (GRCm39)	D204E	possibly damaging	Het
Hsf2	T	A	10: 57,380,739 (GRCm39)	I191N	probably damaging	Het
Hspa12a	T	C	19: 58,788,124 (GRCm39)	D566G	probably benign	Het
Igf1	G	C	10: 87,700,722 (GRCm39)	V49L	probably damaging	Het
Igfbpl1	C	T	4: 45,826,663 (GRCm39)	C44Y	probably damaging	Het
Letm1	G	A	5: 33,939,851 (GRCm39)	R16C	probably benign	Het
Lypd8l	T	A	11: 58,499,314 (GRCm39)	Y168F	probably benign	Het
Marf1	A	G	16: 13,956,384 (GRCm39)	V819A	probably damaging	Het
Mfsd4b4	A	T	10: 39,767,948 (GRCm39)	S428T	probably benign	Het
Myo1d	T	C	11: 80,565,783 (GRCm39)	I347M	probably benign	Het
Myo9b	A	G	8: 71,743,463 (GRCm39)	I175V	probably damaging	Het
Naip5	A	T	13: 100,359,922 (GRCm39)	V438E	probably damaging	Het
Nup205	T	A	6: 35,185,044 (GRCm39)	V768E	possibly damaging	Het
Or4k6	A	T	14: 50,475,567 (GRCm39)	Y258*	probably null	Het
Or9g4b	T	A	2: 85,616,726 (GRCm39)	Y290*	probably null	Het
Pcdh15	C	T	10: 74,481,821 (GRCm39)	H1651Y	possibly damaging	Het
Pdgfra	A	T	5: 75,334,055 (GRCm39)	Q376L	possibly damaging	Het
Pign	T	C	1: 105,481,622 (GRCm39)	I791M	probably benign	Het
Pik3c2b	T	G	1: 132,994,041 (GRCm39)	S2A	possibly damaging	Het
Pip5k1a	A	T	3: 94,975,558 (GRCm39)	I304K	probably damaging	Het
Pkdrej	A	T	15: 85,702,054 (GRCm39)	L1294*	probably null	Het
Pprc1	T	C	19: 46,052,872 (GRCm39)	S797P	probably damaging	Het
Prob1	A	G	18: 35,787,321 (GRCm39)	V311A	probably benign	Het
Prune2	C	A	19: 16,977,385 (GRCm39)	T40K	probably damaging	Het
Rif1	T	G	2: 52,002,703 (GRCm39)	D2052E	probably benign	Het
Sall1	A	G	8: 89,759,519 (GRCm39)	V195A	probably damaging	Het
Scfd1	T	C	12: 51,474,729 (GRCm39)		probably null	Het
Sidt2	A	T	9: 45,864,148 (GRCm39)	N123K	probably benign	Het
Slc22a6	G	A	19: 8,599,460 (GRCm39)	A320T	probably benign	Het
Slc25a10	A	G	11: 120,388,973 (GRCm39)	H279R	probably benign	Het
Slc35b4	A	G	6: 34,135,556 (GRCm39)	V252A	probably benign	Het
Slc46a3	T	C	5: 147,823,150 (GRCm39)	T231A	probably benign	Het
Stxbp1	T	A	2: 32,691,905 (GRCm39)	H429L	probably damaging	Het
Tas2r134	C	T	2: 51,517,782 (GRCm39)	T87I	probably benign	Het
Tcstv6	A	G	13: 120,307,666 (GRCm39)	D20G	possibly damaging	Het
Tdpoz2	A	T	3: 93,559,582 (GRCm39)	L130H	probably damaging	Het
Tmem69	T	C	4: 116,411,921 (GRCm39)		probably null	Het
Tmppe	G	A	9: 114,234,591 (GRCm39)	V297I	probably benign	Het
Ung	G	T	5: 114,269,398 (GRCm39)	A37S	probably benign	Het
Vdac1	T	C	11: 52,277,200 (GRCm39)	Y237H	probably damaging	Het
Vgll4	T	C	6: 114,898,328 (GRCm39)	Y11C	probably damaging	Het
Vmn1r24	A	G	6: 57,933,437 (GRCm39)	I27T	probably benign	Het
Zfp280b	T	A	10: 75,875,522 (GRCm39)	M467K	probably benign	Het
Zkscan4	A	G	13: 21,668,535 (GRCm39)	I329V	probably damaging	Het

Other mutations in Ccm2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02126:Ccm2	APN	11	6,544,154 (GRCm39)	missense	probably damaging	0.97
IGL02274:Ccm2	APN	11	6,540,808 (GRCm39)	missense	probably damaging	1.00
IGL02946:Ccm2	APN	11	6,546,195 (GRCm39)	missense	probably damaging	1.00
IGL02973:Ccm2	APN	11	6,534,544 (GRCm39)	missense	probably damaging	1.00
R0521:Ccm2	UTSW	11	6,540,886 (GRCm39)	missense	probably damaging	1.00
R1024:Ccm2	UTSW	11	6,520,119 (GRCm39)	nonsense	probably null
R1201:Ccm2	UTSW	11	6,543,682 (GRCm39)	missense	probably benign
R1687:Ccm2	UTSW	11	6,535,118 (GRCm39)	missense	probably damaging	1.00
R2199:Ccm2	UTSW	11	6,540,790 (GRCm39)	missense	probably damaging	1.00
R3237:Ccm2	UTSW	11	6,520,090 (GRCm39)	missense	probably benign	0.43
R5196:Ccm2	UTSW	11	6,511,181 (GRCm39)	utr 5 prime	probably benign
R7195:Ccm2	UTSW	11	6,546,302 (GRCm39)	missense	probably damaging	1.00
R7417:Ccm2	UTSW	11	6,543,091 (GRCm39)	missense	probably benign	0.05
R8706:Ccm2	UTSW	11	6,539,447 (GRCm39)	missense	possibly damaging	0.65
R8863:Ccm2	UTSW	11	6,535,211 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GCAGATCTGTGTTTGCCCTG -3'
(R):5'- CCCTTCCAAGTACCTATGCCAG -3'

Sequencing Primer
(F):5'- TCTGTTGGCCCTGATGACAGAC -3'
(R):5'- AGTACCTATGCCAGTCCTGCAG -3'

Posted On

2018-11-28