rs11571651

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000059.4(BRCA2):c.1910-51G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 1,549,260 control chromosomes in the GnomAD database, including 2,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.041 ( 216 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1841 hom. )

Consequence

BRCA2
NM_000059.4 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:9

Conservation

PhyloP100: 0.0290

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-32336214-G-T is Benign according to our data. Variant chr13-32336214-G-T is described in ClinVar as [Benign]. Clinvar id is 209688.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32336214-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4 link	c.1910-51G>T		intron_variant	Intron 10 of 26	ENST00000380152.8	NP_000050.3	P51587

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BRCA2	ENST00000380152.8 link	c.1910-51G>T	intron_variant	Intron 10 of 26	5	NM_000059.4	ENSP00000369497.3	P51587
BRCA2	ENST00000530893.7 link	c.1541-51G>T	intron_variant	Intron 10 of 26	1		ENSP00000499438.2	A0A590UJI7
BRCA2	ENST00000614259.2 link	n.1910-51G>T	intron_variant	Intron 9 of 25	2		ENSP00000506251.1	A0A7P0TAP7

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6210

AN:

152100

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0973

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.0988

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0465

GnomAD3 exomes

AF:

0.0506

AC:

10617

AN:

209908

Hom.:

423

AF XY:

0.0531

AC XY:

6017

AN XY:

113302

show subpopulations

Gnomad AFR exome

AF:

0.0224

Gnomad AMR exome

AF:

0.0724

Gnomad ASJ exome

AF:

0.0364

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.0339

Gnomad OTH exome

AF:

0.0497

GnomAD4 exome

AF:

0.0417

AC:

58223

AN:

1397042

Hom.:

1841

Cov.:

AF XY:

0.0441

AC XY:

30615

AN XY:

694330

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.0760

Gnomad4 ASJ exome

AF:

0.0407

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0152

Gnomad4 NFE exome

AF:

0.0341

Gnomad4 OTH exome

AF:

0.0456

GnomAD4 genome

AF:

0.0409

AC:

6229

AN:

152218

Hom.:

216

Cov.:

AF XY:

0.0436

AC XY:

3242

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.0980

Gnomad4 ASJ

AF:

0.0435

Gnomad4 EAS

AF:

0.0986

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.0344

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0337

Hom.:

Bravo

AF:

0.0422

Asia WGS

AF:

0.110

AC:

381

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2

Benign:3

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 0.1031 (Asian), 0.01423 (African), 0.03694 (European), derived from 1000 genomes (2012-04-30). -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Nov 01, 2017

GeneKor MSA

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:2

Mar 07, 2015

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

DANN

Benign

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over