13-32331082-ATT-AT

Position:

• chr13-32331082-ATT-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000059.4(BRCA2):​c.793+64delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 958,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 32)
  • Exomes 𝑓: 0.061 (0 hom.)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.101

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-32331082-AT-A is Benign according to our data. Variant chr13-32331082-AT-A is described in ClinVar as [Benign]. Clinvar id is 522622.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-32331082-AT-A is described in Lovd as [Benign]. Variant chr13-32331082-AT-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.793+64delT		intron_variant		ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000380152.8	c.793+64delT		intron_variant		5	NM_000059.4	ENSP00000369497.3
BRCA2	ENST00000530893.7	c.424+64delT		intron_variant		1		ENSP00000499438.2
BRCA2	ENST00000614259.2	n.793+64delT		intron_variant		2		ENSP00000506251.1

Frequencies

GnomAD3 genomes AF: 0.000494 AC: 72 AN: 145774 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000892

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.000396

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00343

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000288

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.0609 AC: 49449 AN: 812430 Hom.: 0 AF XY: 0.0613 AC XY: 24874 AN XY: 405640

Gnomad4 AFR exome AF: 0.0672

Gnomad4 AMR exome AF: 0.0866

Gnomad4 ASJ exome AF: 0.0763

Gnomad4 EAS exome AF: 0.0771

Gnomad4 SAS exome AF: 0.0659

Gnomad4 FIN exome AF: 0.0721

Gnomad4 NFE exome AF: 0.0575

Gnomad4 OTH exome AF: 0.0684

GnomAD4 genome AF: 0.000501 AC: 73 AN: 145814 Hom.: 0 Cov.: 32 AF XY: 0.000536 AC XY: 38 AN XY: 70874

Gnomad4 AFR AF: 0.0000998

Gnomad4 AMR AF: 0.000891

Gnomad4 ASJ AF: 0.000295

Gnomad4 EAS AF: 0.000397

Gnomad4 SAS AF: 0.000217

Gnomad4 FIN AF: 0.00343

Gnomad4 NFE AF: 0.000288

Gnomad4 OTH AF: 0.00100

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Dec 03, 2017

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Computational scores

Source: dbNSFP v4.3

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: rs751977993; hg19: chr13-32905219;