chr13-32379251-T-C

Variant names:

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.8755-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,499,332 control chromosomes in the GnomAD database, including 205,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.52 ( 20438 hom., cov: 33)

Exomes 𝑓: 0.52 ( 184643 hom. )

Consequence

BRCA2
NM_000059.4 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:12O:1

Conservation

PhyloP100: -1.18

Publications

95 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):

breast-ovarian cancer, familial, susceptibility to, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
Fanconi anemia complementation group D1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P
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=-0.88).

BP6

Variant 13-32379251-T-C is Benign according to our data. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32379251-T-C is described in CliVar as Benign. Clinvar id is 126190.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4 link	c.8755-66T>C		intron_variant	Intron 21 of 26	ENST00000380152.8	NP_000050.3	P51587

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BRCA2	ENST00000380152.8 link	c.8755-66T>C	intron_variant	Intron 21 of 26	5	NM_000059.4	ENSP00000369497.3	P51587
BRCA2	ENST00000530893.7 link	c.8386-66T>C	intron_variant	Intron 21 of 26	1		ENSP00000499438.2	A0A590UJI7
BRCA2	ENST00000614259.2 link	n.*813-66T>C	intron_variant	Intron 20 of 25	2		ENSP00000506251.1	A0A7P0TAP7

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

78588

AN:

151904

Hom.:

20418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.529

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.571

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.500

GnomAD4 exome

AF:

0.522

AC:

703288

AN:

1347310

Hom.:

184643

AF XY:

0.521

AC XY:

351341

AN XY:

674262

show subpopulations

African (AFR)

AF:

0.489

AC:

15070

AN:

30794

American (AMR)

AF:

0.513

AC:

21766

AN:

42462

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

12000

AN:

25324

East Asian (EAS)

AF:

0.608

AC:

23217

AN:

38160

South Asian (SAS)

AF:

0.489

AC:

39715

AN:

81152

European-Finnish (FIN)

AF:

0.575

AC:

29801

AN:

51848

Middle Eastern (MID)

AF:

0.408

AC:

2267

AN:

5562

European-Non Finnish (NFE)

AF:

0.522

AC:

530380

AN:

1015616

Other (OTH)

AF:

0.516

AC:

29072

AN:

56392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

16217

32435

48652

64870

81087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14870

29740

44610

59480

74350

<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:

0.517

AC:

78659

AN:

152022

Hom.:

20438

Cov.:

AF XY:

0.521

AC XY:

38727

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.501

AC:

20763

AN:

41478

American (AMR)

AF:

0.530

AC:

8097

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

1639

AN:

3470

East Asian (EAS)

AF:

0.570

AC:

2947

AN:

5166

South Asian (SAS)

AF:

0.478

AC:

2301

AN:

4810

European-Finnish (FIN)

AF:

0.573

AC:

6044

AN:

10552

Middle Eastern (MID)

AF:

0.414

AC:

121

AN:

292

European-Non Finnish (NFE)

AF:

0.520

AC:

35305

AN:

67952

Other (OTH)

AF:

0.498

AC:

1050

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1972

3944

5917

7889

9861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.515

Hom.:

94699

Bravo

AF:

0.511

Asia WGS

AF:

0.520

AC:

1809

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2

Benign:4Other:1

Jan 12, 2015

Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.549 (Asian), 0.502 (African), 0.5383 (European), derived from 1000 genomes (2012-04-30). -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breast Cancer Information Core (BIC) (BRCA2)

Significance:not provided

Review Status:no classification provided

Collection Method:clinical testing

- -

GreenArray Genomic Research & Solutions of Accurate Diagnostic Private Limited

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:4

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 01, 2017

GeneKor MSA

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary cancer-predisposing syndrome

Benign:1

Nov 19, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Familial cancer of breast

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.98

(source)

DANN

Benign

0.47

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over