13-32331082-ATT-ATTT

Position:

• chr13-32331082-ATT-ATTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000059.4(BRCA2):​c.793+64dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 974,590 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.075 (0 hom.)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 510 AN: 145896 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00110

Gnomad ASJ AF: 0.000590

Gnomad EAS AF: 0.000396

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.00121

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.000939

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.0749 AC: 62045 AN: 828654 Hom.: 0 AF XY: 0.0754 AC XY: 31204 AN XY: 413694

Gnomad4 AFR exome AF: 0.0900

Gnomad4 AMR exome AF: 0.0778

Gnomad4 ASJ exome AF: 0.0892

Gnomad4 EAS exome AF: 0.0892

Gnomad4 SAS exome AF: 0.0697

Gnomad4 FIN exome AF: 0.0749

Gnomad4 NFE exome AF: 0.0736

Gnomad4 OTH exome AF: 0.0808

GnomAD4 genome AF: 0.00350 AC: 511 AN: 145936 Hom.: 3 Cov.: 32 AF XY: 0.00331 AC XY: 235 AN XY: 70968

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.00110

Gnomad4 ASJ AF: 0.000590

Gnomad4 EAS AF: 0.000595

Gnomad4 SAS AF: 0.000867

Gnomad4 FIN AF: 0.00121

Gnomad4 NFE AF: 0.000939

Gnomad4 OTH AF: 0.00100

ClinVar

Not reported in ClinVar

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;