rs9595456

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000059.4(BRCA2):c.9257-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,473,682 control chromosomes in the GnomAD database, including 757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.041 ( 350 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 407 hom. )

Consequence

BRCA2
NM_000059.4 intron

Scores

Clinical Significance

Benign reviewed by expert panel U:1B:8

Conservation

PhyloP100: -0.949

Publications

8 publications found

Variant links:

Genes affected

BRCA2 (HGNC:1101): (BRCA2 DNA repair associated) 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 largest exon in both genes is exon 11, which harbors the most important and frequent mutations in breast cancer patients. The BRCA2 gene was found on chromosome 13q12.3 in human. 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, May 2020]

BRCA2 Gene-Disease associations (from GenCC):

BRCA2-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
breast-ovarian cancer, familial, susceptibility to, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Fanconi anemia complementation group D1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
pancreatic cancer, susceptibility to, 2
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary breast ovarian cancer syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
medulloblastoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BRCA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 13-32394606-G-A is Benign according to our data. Variant chr13-32394606-G-A is described in ClinVar as Benign. ClinVar VariationId is 126207.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000059.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA2	NM_000059.4	MANE Select	c.9257-83G>A	intron	N/A	NP_000050.3	A0A7P0T9D7
BRCA2	NM_001432077.1		c.9257-83G>A	intron	N/A	NP_001419006.1	A0A7P0T9D7
BRCA2	NM_001406720.1		c.9206-83G>A	intron	N/A	NP_001393649.1	A0A8V8TPZ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRCA2	ENST00000380152.8	TSL:5 MANE Select	c.9257-83G>A	intron	N/A	ENSP00000369497.3	P51587
BRCA2	ENST00000544455.6	TSL:1	c.9257-83G>A	intron	N/A	ENSP00000439902.1	P51587
BRCA2	ENST00000530893.7	TSL:1	c.8888-83G>A	intron	N/A	ENSP00000499438.2	A0A590UJI7

Frequencies

GnomAD3 genomes

AF:

0.0405

AC:

6156

AN:

152114

Hom.:

346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0471

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00877

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.0350

GnomAD4 exome

AF:

0.00747

AC:

9876

AN:

1321450

Hom.:

407

AF XY:

0.00681

AC XY:

4496

AN XY:

659880

show subpopulations

African (AFR)

AF:

0.131

AC:

3912

AN:

29940

American (AMR)

AF:

0.0769

AC:

2793

AN:

36324

Ashkenazi Jewish (ASJ)

AF:

0.000612

AC:

AN:

24498

East Asian (EAS)

AF:

0.0212

AC:

824

AN:

38860

South Asian (SAS)

AF:

0.00235

AC:

181

AN:

76884

European-Finnish (FIN)

AF:

0.00690

AC:

312

AN:

45204

Middle Eastern (MID)

AF:

0.0172

AC:

AN:

3828

European-Non Finnish (NFE)

AF:

0.00104

AC:

1047

AN:

1010526

Other (OTH)

AF:

0.0131

AC:

726

AN:

55386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

453

905

1358

1810

2263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0405

AC:

6169

AN:

152232

Hom.:

350

Cov.:

AF XY:

0.0405

AC XY:

3012

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.121

AC:

5025

AN:

41542

American (AMR)

AF:

0.0474

AC:

724

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.0233

AC:

121

AN:

5184

South Asian (SAS)

AF:

0.00332

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00877

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00160

AC:

109

AN:

68020

Other (OTH)

AF:

0.0346

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

291

582

872

1163

1454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0408

Hom.:

Bravo

AF:

0.0498

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Breast-ovarian cancer, familial, susceptibility to, 2 (4)

not provided (2)

not specified (2)

Familial cancer of breast (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.8

(source)

DANN

Benign

0.69

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over