Mutagenetix > Incidental Mutation

Incidental Mutation 'R6508:Brca2'

523988

Institutional Source

Beutler Lab

Gene Symbol

Brca2

Ensembl Gene

ENSMUSG00000041147

Gene Name

breast cancer 2, early onset

Synonyms

Fancd1, RAB163

MMRRC Submission

044638-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6508 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

150446095-150493794 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 150460058 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Aspartic acid at position 444 (E444D)

Ref Sequence

ENSEMBL: ENSMUSP00000144150 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000044620] [ENSMUST00000202003] [ENSMUST00000202313]

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000044620
AA Change: E444D

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000038576
Gene: ENSMUSG00000041147
AA Change: E444D

Domain	Start	End	E-Value	Type
low complexity region	36	51	N/A	INTRINSIC
low complexity region	100	123	N/A	INTRINSIC
low complexity region	187	199	N/A	INTRINSIC
low complexity region	746	761	N/A	INTRINSIC
low complexity region	904	917	N/A	INTRINSIC
Pfam:BRCA2	982	1014	2.6e-13	PFAM
Pfam:BRCA2	1193	1225	3.9e-16	PFAM
low complexity region	1239	1252	N/A	INTRINSIC
Pfam:BRCA2	1395	1425	1.4e-13	PFAM
Pfam:BRCA2	1492	1524	1.8e-13	PFAM
Pfam:BRCA2	1624	1655	8.4e-12	PFAM
Pfam:BRCA2	1925	1957	8e-15	PFAM
Pfam:BRCA2	2005	2037	1.7e-11	PFAM
Pfam:BRCA-2_helical	2402	2588	1.3e-94	PFAM
Pfam:BRCA-2_OB1	2591	2717	5.3e-44	PFAM
Tower	2752	2793	2.37e-18	SMART
Pfam:BRCA-2_OB3	2971	3104	1.5e-49	PFAM
low complexity region	3197	3208	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000201149

Predicted Effect

probably benign
Transcript: ENSMUST00000202003
AA Change: E444D

PolyPhen 2 Score 0.374 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000144676
Gene: ENSMUSG00000041147
AA Change: E444D

Domain	Start	End	E-Value	Type
low complexity region	36	51	N/A	INTRINSIC
low complexity region	100	123	N/A	INTRINSIC
low complexity region	187	199	N/A	INTRINSIC
low complexity region	746	761	N/A	INTRINSIC
low complexity region	904	917	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000202313
AA Change: E444D

PolyPhen 2 Score 0.907 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000144150
Gene: ENSMUSG00000041147
AA Change: E444D

Domain	Start	End	E-Value	Type
low complexity region	36	51	N/A	INTRINSIC
low complexity region	100	123	N/A	INTRINSIC
low complexity region	187	199	N/A	INTRINSIC
low complexity region	746	761	N/A	INTRINSIC
low complexity region	904	917	N/A	INTRINSIC
Pfam:BRCA2	982	1014	2.6e-13	PFAM
Pfam:BRCA2	1193	1225	3.9e-16	PFAM
low complexity region	1239	1252	N/A	INTRINSIC
Pfam:BRCA2	1395	1425	1.4e-13	PFAM
Pfam:BRCA2	1492	1524	1.8e-13	PFAM
Pfam:BRCA2	1624	1655	8.4e-12	PFAM
Pfam:BRCA2	1925	1957	8e-15	PFAM
Pfam:BRCA2	2005	2037	1.7e-11	PFAM
Pfam:BRCA-2_helical	2402	2588	1.3e-94	PFAM
Pfam:BRCA-2_OB1	2591	2717	5.3e-44	PFAM
Tower	2752	2793	2.37e-18	SMART
Pfam:BRCA-2_OB3	2971	3104	1.5e-49	PFAM
low complexity region	3197	3208	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000202975

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.0%
20x: 94.2%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, Dec 2008]
PHENOTYPE: Homozygous null mutants are embryonic lethal with abnormalities including growth retardation, neural tube defects, and mesoderm abnormalities; conditional mutations cause genetic instability and enhanced tumor formation; mutants with truncated BRCA2 protein survive, are small, infertile, show improper tissue differentiation and develop lymphomas and carcinomas. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 45 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aadacl4fm2	G	A	4: 144,291,590 (GRCm39)	R39*	probably null	Het
Camkk2	G	T	5: 122,884,382 (GRCm39)	N346K	probably damaging	Het
Car4	C	A	11: 84,856,469 (GRCm39)	D252E	possibly damaging	Het
Chd1	A	G	17: 15,958,895 (GRCm39)	K649R	probably benign	Het
Col12a1	A	G	9: 79,557,231 (GRCm39)	Y1966H	probably damaging	Het
Crppa	C	T	12: 36,476,298 (GRCm39)	A180V	possibly damaging	Het
Cts6	T	A	13: 61,344,221 (GRCm39)	H277L	probably damaging	Het
Dcc	G	T	18: 71,439,144 (GRCm39)	P1246Q	probably damaging	Het
Dlg5	G	A	14: 24,188,774 (GRCm39)	T1739I	probably benign	Het
Eci1	T	A	17: 24,656,283 (GRCm39)	N164K	probably damaging	Het
Entpd7	G	A	19: 43,679,525 (GRCm39)	R26H	probably damaging	Het
Fanci	A	G	7: 79,093,516 (GRCm39)	K1008E	probably damaging	Het
Htr2b	T	C	1: 86,030,186 (GRCm39)	T170A	possibly damaging	Het
Irgm2	A	G	11: 58,110,327 (GRCm39)	E18G	probably benign	Het
Kdm1a	A	T	4: 136,281,621 (GRCm39)	V630E	probably damaging	Het
Keap1	G	A	9: 21,143,010 (GRCm39)	T501I	possibly damaging	Het
L3mbtl3	T	A	10: 26,194,325 (GRCm39)	H424L	unknown	Het
Lrrc14b	C	T	13: 74,511,337 (GRCm39)	D248N	possibly damaging	Het
Macf1	T	A	4: 123,363,535 (GRCm39)	D3364V	probably damaging	Het
Map3k20	G	A	2: 72,272,253 (GRCm39)	G794S	probably benign	Het
Mcat	T	C	15: 83,433,452 (GRCm39)	Q34R	probably benign	Het
Mettl4	T	C	17: 95,051,373 (GRCm39)	E148G	probably damaging	Het
Mgat3	T	C	15: 80,096,225 (GRCm39)	S351P	possibly damaging	Het
Mllt1	A	T	17: 57,234,054 (GRCm39)	I44N	probably damaging	Het
Mlxipl	G	T	5: 135,157,474 (GRCm39)	A337S	probably benign	Het
Naip1	A	G	13: 100,572,973 (GRCm39)	F254L	probably damaging	Het
Obscn	A	T	11: 58,944,973 (GRCm39)		probably null	Het
Or10q1	C	T	19: 13,726,718 (GRCm39)	P83S	probably damaging	Het
Pcdh12	G	A	18: 38,414,390 (GRCm39)	R912*	probably null	Het
Pcdh17	A	G	14: 84,685,419 (GRCm39)	N629D	probably damaging	Het
Pcnx1	T	C	12: 81,959,479 (GRCm39)	I170T	probably damaging	Het
Pgr	A	G	9: 8,956,290 (GRCm39)	Y746C	probably damaging	Het
Pramel29	A	T	4: 143,934,171 (GRCm39)	L312*	probably null	Het
Pum2	T	C	12: 8,798,861 (GRCm39)	Y991H	probably benign	Het
Rcc1l	A	T	5: 134,198,077 (GRCm39)	V185D	probably damaging	Het
Scarb1	A	T	5: 125,381,389 (GRCm39)	S52T	possibly damaging	Het
Smc1b	C	T	15: 84,976,232 (GRCm39)	R825Q	probably benign	Het
Spata4	T	C	8: 55,053,887 (GRCm39)	S18P	probably benign	Het
Stard13	G	A	5: 150,986,754 (GRCm39)	T134I	probably benign	Het
Tbc1d32	C	T	10: 56,100,786 (GRCm39)	C64Y	probably damaging	Het
Tll1	T	G	8: 64,551,494 (GRCm39)	I296L	probably damaging	Het
Tmem229b	T	G	12: 79,011,680 (GRCm39)	T84P	probably damaging	Het
Ttn	T	C	2: 76,544,757 (GRCm39)	T32782A	possibly damaging	Het
Vmn1r73	G	A	7: 11,490,631 (GRCm39)	V150I	possibly damaging	Het
Vmn2r80	T	A	10: 79,030,290 (GRCm39)	F705L	probably benign	Het

Other mutations in Brca2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00332:Brca2	APN	5	150,463,363 (GRCm39)	missense	probably benign	0.18
IGL00392:Brca2	APN	5	150,464,705 (GRCm39)	missense	probably benign	0.02
IGL00557:Brca2	APN	5	150,484,003 (GRCm39)	missense	probably benign
IGL00798:Brca2	APN	5	150,462,928 (GRCm39)	missense	probably benign	0.30
IGL00933:Brca2	APN	5	150,465,869 (GRCm39)	missense	probably benign	0.04
IGL00964:Brca2	APN	5	150,455,775 (GRCm39)	missense	probably damaging	1.00
IGL01152:Brca2	APN	5	150,465,855 (GRCm39)	missense	probably damaging	0.99
IGL01577:Brca2	APN	5	150,465,085 (GRCm39)	nonsense	probably null
IGL01585:Brca2	APN	5	150,462,981 (GRCm39)	missense	possibly damaging	0.76
IGL01732:Brca2	APN	5	150,465,852 (GRCm39)	missense	probably benign	0.13
IGL01809:Brca2	APN	5	150,454,526 (GRCm39)	splice site	probably null
IGL01911:Brca2	APN	5	150,491,078 (GRCm39)	missense	probably damaging	0.96
IGL02113:Brca2	APN	5	150,464,444 (GRCm39)	missense	possibly damaging	0.95
IGL02313:Brca2	APN	5	150,462,126 (GRCm39)	missense	probably damaging	1.00
IGL02342:Brca2	APN	5	150,466,289 (GRCm39)	missense	possibly damaging	0.94
IGL02508:Brca2	APN	5	150,466,773 (GRCm39)	missense	possibly damaging	0.85
IGL02532:Brca2	APN	5	150,474,327 (GRCm39)	missense	probably damaging	1.00
IGL02646:Brca2	APN	5	150,484,255 (GRCm39)	missense	possibly damaging	0.89
IGL02738:Brca2	APN	5	150,490,500 (GRCm39)	missense	probably damaging	1.00
IGL02833:Brca2	APN	5	150,465,255 (GRCm39)	missense	possibly damaging	0.83
IGL02871:Brca2	APN	5	150,466,017 (GRCm39)	missense	probably benign	0.13
IGL02995:Brca2	APN	5	150,452,953 (GRCm39)	missense	probably damaging	1.00
IGL03105:Brca2	APN	5	150,483,950 (GRCm39)	missense	probably benign	0.02
BB007:Brca2	UTSW	5	150,481,975 (GRCm39)	missense	probably damaging	0.96
BB017:Brca2	UTSW	5	150,481,975 (GRCm39)	missense	probably damaging	0.96
R0219:Brca2	UTSW	5	150,446,640 (GRCm39)	splice site	probably benign
R0416:Brca2	UTSW	5	150,492,857 (GRCm39)	missense	possibly damaging	0.93
R0441:Brca2	UTSW	5	150,465,322 (GRCm39)	missense	probably damaging	0.96
R0548:Brca2	UTSW	5	150,468,400 (GRCm39)	missense	probably damaging	0.96
R0745:Brca2	UTSW	5	150,468,347 (GRCm39)	splice site	probably benign
R0799:Brca2	UTSW	5	150,483,658 (GRCm39)	missense	probably damaging	0.99
R1165:Brca2	UTSW	5	150,466,212 (GRCm39)	missense	probably damaging	0.98
R1247:Brca2	UTSW	5	150,464,739 (GRCm39)	missense	probably damaging	1.00
R1403:Brca2	UTSW	5	150,466,114 (GRCm39)	missense	probably benign	0.22
R1403:Brca2	UTSW	5	150,466,114 (GRCm39)	missense	probably benign	0.22
R1444:Brca2	UTSW	5	150,465,915 (GRCm39)	missense	probably benign
R1466:Brca2	UTSW	5	150,475,723 (GRCm39)	missense	probably damaging	0.99
R1466:Brca2	UTSW	5	150,475,723 (GRCm39)	missense	probably damaging	0.99
R1584:Brca2	UTSW	5	150,475,723 (GRCm39)	missense	probably damaging	0.99
R1599:Brca2	UTSW	5	150,472,178 (GRCm39)	nonsense	probably null
R1600:Brca2	UTSW	5	150,484,295 (GRCm39)	splice site	probably benign
R1822:Brca2	UTSW	5	150,463,663 (GRCm39)	missense	probably benign	0.06
R1824:Brca2	UTSW	5	150,460,387 (GRCm39)	missense	possibly damaging	0.94
R2037:Brca2	UTSW	5	150,464,134 (GRCm39)	missense	probably benign
R2131:Brca2	UTSW	5	150,480,594 (GRCm39)	missense	probably damaging	1.00
R2203:Brca2	UTSW	5	150,462,967 (GRCm39)	missense	possibly damaging	0.58
R2208:Brca2	UTSW	5	150,455,809 (GRCm39)	missense	probably damaging	0.96
R2293:Brca2	UTSW	5	150,483,999 (GRCm39)	missense	possibly damaging	0.86
R2517:Brca2	UTSW	5	150,463,137 (GRCm39)	missense	probably benign	0.04
R2566:Brca2	UTSW	5	150,465,227 (GRCm39)	missense	probably benign	0.03
R3422:Brca2	UTSW	5	150,466,586 (GRCm39)	missense	possibly damaging	0.91
R3917:Brca2	UTSW	5	150,464,292 (GRCm39)	missense	probably damaging	0.96
R3946:Brca2	UTSW	5	150,460,169 (GRCm39)	missense	probably damaging	0.96
R4176:Brca2	UTSW	5	150,463,098 (GRCm39)	nonsense	probably null
R4255:Brca2	UTSW	5	150,464,634 (GRCm39)	missense	possibly damaging	0.92
R4450:Brca2	UTSW	5	150,459,518 (GRCm39)	missense	probably damaging	0.96
R4603:Brca2	UTSW	5	150,459,630 (GRCm39)	missense	possibly damaging	0.86
R4681:Brca2	UTSW	5	150,475,863 (GRCm39)	splice site	probably null
R4755:Brca2	UTSW	5	150,483,452 (GRCm39)	splice site	probably null
R4762:Brca2	UTSW	5	150,454,581 (GRCm39)	missense	probably benign	0.00
R4824:Brca2	UTSW	5	150,463,200 (GRCm39)	missense	probably damaging	1.00
R4887:Brca2	UTSW	5	150,480,402 (GRCm39)	missense	probably damaging	1.00
R5020:Brca2	UTSW	5	150,483,901 (GRCm39)	missense	probably damaging	1.00
R5159:Brca2	UTSW	5	150,465,573 (GRCm39)	missense	possibly damaging	0.93
R5216:Brca2	UTSW	5	150,466,445 (GRCm39)	missense	probably damaging	0.99
R5269:Brca2	UTSW	5	150,462,688 (GRCm39)	missense	possibly damaging	0.75
R5274:Brca2	UTSW	5	150,463,154 (GRCm39)	missense	probably benign	0.00
R5589:Brca2	UTSW	5	150,480,597 (GRCm39)	missense	possibly damaging	0.67
R5619:Brca2	UTSW	5	150,480,579 (GRCm39)	missense	probably damaging	0.96
R5641:Brca2	UTSW	5	150,480,364 (GRCm39)	missense	probably damaging	1.00
R5686:Brca2	UTSW	5	150,464,369 (GRCm39)	missense	probably benign	0.00
R5730:Brca2	UTSW	5	150,492,470 (GRCm39)	missense	possibly damaging	0.85
R5763:Brca2	UTSW	5	150,471,471 (GRCm39)	missense	possibly damaging	0.85
R5877:Brca2	UTSW	5	150,466,686 (GRCm39)	missense	possibly damaging	0.53
R5893:Brca2	UTSW	5	150,492,603 (GRCm39)	missense	probably benign	0.02
R5900:Brca2	UTSW	5	150,464,597 (GRCm39)	missense	probably benign	0.01
R5926:Brca2	UTSW	5	150,458,087 (GRCm39)	missense	probably benign	0.07
R5966:Brca2	UTSW	5	150,466,716 (GRCm39)	missense	probably damaging	0.99
R6025:Brca2	UTSW	5	150,465,040 (GRCm39)	frame shift	probably null
R6062:Brca2	UTSW	5	150,480,354 (GRCm39)	missense	probably damaging	0.96
R6141:Brca2	UTSW	5	150,464,102 (GRCm39)	missense	possibly damaging	0.91
R6244:Brca2	UTSW	5	150,490,443 (GRCm39)	missense	probably benign	0.08
R6519:Brca2	UTSW	5	150,464,444 (GRCm39)	missense	probably damaging	0.99
R6611:Brca2	UTSW	5	150,459,658 (GRCm39)	missense	probably damaging	0.99
R6698:Brca2	UTSW	5	150,455,859 (GRCm39)	missense	probably damaging	1.00
R6856:Brca2	UTSW	5	150,463,673 (GRCm39)	missense	possibly damaging	0.68
R6912:Brca2	UTSW	5	150,465,207 (GRCm39)	missense	probably damaging	0.99
R7002:Brca2	UTSW	5	150,463,383 (GRCm39)	missense	probably benign
R7025:Brca2	UTSW	5	150,463,943 (GRCm39)	missense	probably benign	0.39
R7151:Brca2	UTSW	5	150,464,901 (GRCm39)	missense	probably benign	0.12
R7202:Brca2	UTSW	5	150,455,819 (GRCm39)	missense	probably benign	0.03
R7365:Brca2	UTSW	5	150,455,802 (GRCm39)	missense	probably damaging	0.99
R7510:Brca2	UTSW	5	150,460,156 (GRCm39)	missense	possibly damaging	0.85
R7612:Brca2	UTSW	5	150,464,076 (GRCm39)	missense	probably benign	0.03
R7682:Brca2	UTSW	5	150,466,618 (GRCm39)	missense	probably benign
R7890:Brca2	UTSW	5	150,462,846 (GRCm39)	missense	possibly damaging	0.83
R7930:Brca2	UTSW	5	150,481,975 (GRCm39)	missense	probably damaging	0.96
R7940:Brca2	UTSW	5	150,462,198 (GRCm39)	missense	probably benign
R8054:Brca2	UTSW	5	150,459,969 (GRCm39)	missense	probably benign	0.02
R8056:Brca2	UTSW	5	150,492,771 (GRCm39)	missense	possibly damaging	0.85
R8080:Brca2	UTSW	5	150,463,357 (GRCm39)	missense	probably benign	0.11
R8094:Brca2	UTSW	5	150,459,634 (GRCm39)	missense	possibly damaging	0.85
R8306:Brca2	UTSW	5	150,460,128 (GRCm39)	missense	possibly damaging	0.91
R8401:Brca2	UTSW	5	150,475,817 (GRCm39)	missense	probably damaging	1.00
R8523:Brca2	UTSW	5	150,483,613 (GRCm39)	missense	possibly damaging	0.75
R8784:Brca2	UTSW	5	150,472,126 (GRCm39)	nonsense	probably null
R8791:Brca2	UTSW	5	150,466,061 (GRCm39)	missense	possibly damaging	0.92
R8832:Brca2	UTSW	5	150,465,611 (GRCm39)	missense	possibly damaging	0.91
R8838:Brca2	UTSW	5	150,465,005 (GRCm39)	missense	possibly damaging	0.91
R8845:Brca2	UTSW	5	150,466,847 (GRCm39)	missense	possibly damaging	0.85
R8898:Brca2	UTSW	5	150,492,498 (GRCm39)	missense	possibly damaging	0.53
R8914:Brca2	UTSW	5	150,465,208 (GRCm39)	missense	probably damaging	0.96
R8935:Brca2	UTSW	5	150,492,446 (GRCm39)	missense	possibly damaging	0.70
R9014:Brca2	UTSW	5	150,465,219 (GRCm39)	missense	probably benign
R9023:Brca2	UTSW	5	150,465,360 (GRCm39)	missense	probably benign	0.07
R9094:Brca2	UTSW	5	150,475,770 (GRCm39)	missense	probably benign	0.08
R9195:Brca2	UTSW	5	150,463,418 (GRCm39)	missense	possibly damaging	0.83
R9198:Brca2	UTSW	5	150,459,977 (GRCm39)	missense	possibly damaging	0.91
R9314:Brca2	UTSW	5	150,474,359 (GRCm39)	missense	probably damaging	0.96
R9408:Brca2	UTSW	5	150,464,982 (GRCm39)	missense	probably damaging	1.00
R9459:Brca2	UTSW	5	150,464,094 (GRCm39)	missense	probably damaging	0.98
R9512:Brca2	UTSW	5	150,454,546 (GRCm39)	missense	probably benign	0.40
R9622:Brca2	UTSW	5	150,480,410 (GRCm39)	missense	probably damaging	0.96
R9777:Brca2	UTSW	5	150,480,579 (GRCm39)	missense	probably damaging	0.99
Z1088:Brca2	UTSW	5	150,466,228 (GRCm39)	missense	probably damaging	0.96
Z1186:Brca2	UTSW	5	150,460,048 (GRCm39)	missense	probably damaging	0.98

Predicted Primers

PCR Primer
(F):5'- CAGCCAGAATGAGGAAATCTGC -3'
(R):5'- AAAGTCTCGTCAAGTGGCTCTC -3'

Sequencing Primer
(F):5'- CTGCAATGAAGCTGTACAGTGTTCAG -3'
(R):5'- GTGGCTCTCTCATCTTGAATATAGAC -3'

Posted On

2018-06-22