Mutagenetix > Incidental Mutation

Incidental Mutation 'R7195:Ccm2'

559869

Institutional Source

Beutler Lab

Gene Symbol

Ccm2

Ensembl Gene

ENSMUSG00000000378

Gene Name

cerebral cavernous malformation 2

Synonyms

MMRRC Submission

045336-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7195 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

6496887-6546744 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 6546302 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 435 (S435P)

Ref Sequence

ENSEMBL: ENSMUSP00000000388 (fasta)

Gene Model

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

AlphaFold

Q8K2Y9

Predicted Effect

probably damaging
Transcript: ENSMUST00000000388
AA Change: S435P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000000388
Gene: ENSMUSG00000000378
AA Change: S435P

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

probably damaging
Transcript: ENSMUST00000109721
AA Change: S371P

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000105343
Gene: ENSMUSG00000000378
AA Change: S371P

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 damaging
Transcript: ENSMUST00000109722
AA Change: S371P

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000105344
Gene: ENSMUSG00000000378
AA Change: S371P

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: 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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.8%

Validation Efficiency

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: 64 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930438A08Rik	T	C	11: 58,179,242 (GRCm39)		probably null	Het
Abca2	A	G	2: 25,332,088 (GRCm39)	D1400G	probably benign	Het
Actl11	A	T	9: 107,806,069 (GRCm39)	K131*	probably null	Het
Adam39	A	T	8: 41,277,812 (GRCm39)	R68*	probably null	Het
Akap7	A	T	10: 25,147,405 (GRCm39)	N108K	probably damaging	Het
Arhgef10l	C	A	4: 140,338,721 (GRCm39)	A14S	probably benign	Het
Ccdc141	T	G	2: 76,879,927 (GRCm39)	N632T	probably benign	Het
Cd36	A	G	5: 18,019,187 (GRCm39)	L178P	probably damaging	Het
Cd7	T	C	11: 120,929,075 (GRCm39)	I59V	probably benign	Het
Cds2	T	A	2: 132,135,204 (GRCm39)	S32T	probably benign	Het
Cep19	A	G	16: 31,925,904 (GRCm39)	D104G	probably damaging	Het
Col1a2	C	T	6: 4,510,753 (GRCm39)	P68S	unknown	Het
Col20a1	A	G	2: 180,649,024 (GRCm39)	H1011R	probably damaging	Het
Cspg4b	A	T	13: 113,504,463 (GRCm39)	D1864V		Het
D7Ertd443e	A	G	7: 133,896,851 (GRCm39)	V513A	probably damaging	Het
Egfr	C	T	11: 16,818,162 (GRCm39)	P228L	probably damaging	Het
Fam243	C	T	16: 92,118,037 (GRCm39)	V84M	probably damaging	Het
Fam78b	A	G	1: 166,906,131 (GRCm39)	R97G	probably damaging	Het
Flt1	C	T	5: 147,540,386 (GRCm39)	V768M	probably damaging	Het
Gdap1l1	A	T	2: 163,288,050 (GRCm39)	N96Y	probably damaging	Het
Gm7168	T	A	17: 14,169,622 (GRCm39)	Y330N	probably benign	Het
Hnrnpul1	T	C	7: 25,424,203 (GRCm39)	N683S	unknown	Het
Ice2	C	T	9: 69,335,782 (GRCm39)	P922S	possibly damaging	Het
Iglv2	A	G	16: 19,079,260 (GRCm39)	V81A	not run	Het
Irs1	A	G	1: 82,265,177 (GRCm39)	I1013T	probably benign	Het
Itih4	T	C	14: 30,621,432 (GRCm39)	S832P	probably damaging	Het
Klhl1	A	T	14: 96,517,513 (GRCm39)	Y388N	probably benign	Het
Lrrc37a	G	A	11: 103,348,601 (GRCm39)	S2698L	unknown	Het
Map4k4	T	C	1: 40,058,829 (GRCm39)	Y1008H	possibly damaging	Het
Mdn1	G	T	4: 32,701,823 (GRCm39)	G1519W	probably damaging	Het
Mga	T	A	2: 119,747,809 (GRCm39)	D653E	probably damaging	Het
Npas1	T	C	7: 16,208,733 (GRCm39)	E48G	probably damaging	Het
Nup188	G	A	2: 30,231,842 (GRCm39)		probably null	Het
Or1p1b	G	T	11: 74,130,394 (GRCm39)	M1I	probably null	Het
Or3a4	T	A	11: 73,945,223 (GRCm39)	M121L	probably damaging	Het
Or4c110	G	A	2: 88,832,075 (GRCm39)	L186F		Het
Or51a39	A	G	7: 102,362,873 (GRCm39)	V249A	possibly damaging	Het
Or55b4	A	T	7: 102,133,574 (GRCm39)	V251D	probably damaging	Het
Or7h8	A	G	9: 20,123,840 (GRCm39)	N65S	probably damaging	Het
Oxct1	T	C	15: 4,158,383 (GRCm39)	V439A	probably damaging	Het
Pcdhb22	G	T	18: 37,652,341 (GRCm39)	G13W	probably damaging	Het
Pex11g	A	G	8: 3,509,237 (GRCm39)	V230A	probably benign	Het
Pop1	C	T	15: 34,510,525 (GRCm39)	S439L	probably damaging	Het
Ptpn9	T	A	9: 56,929,533 (GRCm39)	H83Q	probably benign	Het
Qrfp	C	T	2: 31,698,704 (GRCm39)	R76H	probably benign	Het
Slc30a3	A	G	5: 31,246,139 (GRCm39)	V197A	probably benign	Het
Slc8a3	T	C	12: 81,361,047 (GRCm39)	N591D	possibly damaging	Het
Sp4	G	T	12: 118,263,807 (GRCm39)	Q80K	possibly damaging	Het
Spock1	C	T	13: 58,055,316 (GRCm39)	G29D	possibly damaging	Het
Sprr1a	G	T	3: 92,391,674 (GRCm39)	P109Q	probably damaging	Het
Suz12	T	A	11: 79,904,309 (GRCm39)	F239L	probably damaging	Het
Tbx3	A	G	5: 119,813,648 (GRCm39)	Y248C	probably damaging	Het
Trabd2b	T	C	4: 114,266,637 (GRCm39)	L217P	probably damaging	Het
Ubxn11	A	C	4: 133,853,726 (GRCm39)	I398L	possibly damaging	Het
Vmn1r173	T	A	7: 23,401,884 (GRCm39)	S40T	probably damaging	Het
Vmn2r2	T	C	3: 64,023,900 (GRCm39)	S894G	probably benign	Het
Vmn2r65	A	G	7: 84,592,347 (GRCm39)		probably null	Het
Vps13c	G	A	9: 67,853,107 (GRCm39)	G2400D	possibly damaging	Het
Vps8	T	C	16: 21,275,032 (GRCm39)	Y197H	probably damaging	Het
Wdr91	T	C	6: 34,866,209 (GRCm39)	N486D	possibly damaging	Het
Wwp1	A	G	4: 19,627,908 (GRCm39)	I695T	possibly damaging	Het
Zc3hc1	T	C	6: 30,382,547 (GRCm39)	D133G	probably benign	Het
Zcchc14	T	C	8: 122,335,200 (GRCm39)	I307V	unknown	Het
Zfp933	G	A	4: 147,910,636 (GRCm39)	T320I	probably benign	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
R6954:Ccm2	UTSW	11	6,544,239 (GRCm39)	missense	probably damaging	0.98
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'- AGCACTTTGAAAACTTCCTGGAG -3'
(R):5'- TCCTTCACAGTAGAGGACCTG -3'

Sequencing Primer
(F):5'- AACTTCCTGGAGACCATTGG -3'
(R):5'- ACAGTAGAGGACCTGGCCAC -3'

Posted On

2019-06-26