chr13-32345500-T-G

Position:

• chr13-32345500-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000059.4(BRCA2):​c.6937+847T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,782 control chromosomes in the GnomAD database, including 6,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.29 (6489 hom., cov: 32)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign reviewed by expert panel B:7
• Conservation: PhyloP100: -0.260

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-32345500-T-G is Benign according to our data. Variant chr13-32345500-T-G is described in ClinVar as [Benign]. Clinvar id is 209708.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32345500-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRCA2	NM_000059.4	c.6937+847T>G		intron_variant		ENST00000380152.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRCA2	ENST00000380152.8	c.6937+847T>G		intron_variant		5	NM_000059.4	A2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43795 AN: 151664 Hom.: 6491 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 43790 AN: 151782 Hom.: 6489 Cov.: 32 AF XY: 0.290 AC XY: 21491 AN XY: 74176

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.280

Alfa AF: 0.309 Hom.: 973

Bravo AF: 0.279

Asia WGS AF: 0.281 AC: 974 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: reviewed by expert panel

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 13, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 22513257) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Breast-ovarian cancer, familial, susceptibility to, 2 Benign:1

Benign, reviewed by expert panel

curation

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

Jan 12, 2015

Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.3829 (Asian), 0.1728 (African), 0.2942 (European), derived from 1000 genomes (2012-04-30). -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Dec 06, 2014

- -

Hereditary breast ovarian cancer syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs9567576; hg19: chr13-32919637;