dbSNP rs11571661: BRCA2:c.6841+80_6841+83delTTAA (chr13-32341273-CAATT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000059.4(BRCA2):c.6841+80_6841+83delTTAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,594,908 control chromosomes in the GnomAD database, including 74,988 homozygotes. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.28 ( 6125 hom., cov: 19)

Exomes 𝑓: 0.31 ( 68863 hom. )

Consequence

BRCA2
NM_000059.4 intron

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel U:2B:7O:1

Conservation

PhyloP100: 0.759

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 13-32341273-CAATT-C is Benign according to our data. Variant chr13-32341273-CAATT-C is described in ClinVar as [Benign]. Clinvar id is 126122.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32341273-CAATT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4 link	c.6841+80_6841+83delTTAA		intron_variant	Intron 11 of 26	ENST00000380152.8	NP_000050.3	P51587

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BRCA2	ENST00000380152.8 link	c.6841+78_6841+81delAATT	intron_variant	Intron 11 of 26	5	NM_000059.4	ENSP00000369497.3	P51587
BRCA2	ENST00000530893.7 link	c.6472+78_6472+81delAATT	intron_variant	Intron 11 of 26	1		ENSP00000499438.2	A0A590UJI7
BRCA2	ENST00000614259.2 link	n.6841+78_6841+81delAATT	intron_variant	Intron 10 of 25	2		ENSP00000506251.1	A0A7P0TAP7

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42671

AN:

151646

Hom.:

6128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.295

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.275

GnomAD4 exome

AF:

0.306

AC:

441481

AN:

1443142

Hom.:

68863

AF XY:

0.307

AC XY:

220348

AN XY:

718630

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.305

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.281

AC:

42663

AN:

151766

Hom.:

6125

Cov.:

AF XY:

0.282

AC XY:

20942

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.222

Gnomad4 ASJ

AF:

0.306

Gnomad4 EAS

AF:

0.394

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.315

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.174

Hom.:

378

Bravo

AF:

0.272

Asia WGS

AF:

0.278

AC:

968

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:2Benign:7Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2

Uncertain:1Benign:3

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 17, 2010

Breast Cancer Information Core (BIC) (BRCA2)

Significance: Uncertain significance

Review Status: no assertion criteria provided

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 0.38 (Asian), 0.18 (African), 0.29 (European), derived from 1000 genomes (2012-04-30). -

Dec 03, 2017

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Uncertain:1Benign:2

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 20, 2017

Department of Pathology and Molecular Medicine, Queen's University

Significance: Uncertain significance

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:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Mar 10, 2015

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial cancer of breast

Other:1

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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