13-32316589-T-G

Position:

• chr13-32316589-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000059.4(BRCA2):​c.67+62T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,469,116 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (20 hom.)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:10
• Conservation: PhyloP100: 3.54

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-32316589-T-G is Benign according to our data. Variant chr13-32316589-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 125991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-32316589-T-G is described in Lovd as [Benign]. Variant chr13-32316589-T-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0026 (3419/1316910) while in subpopulation MID AF= 0.0229 (104/4536). AF 95% confidence interval is 0.0194. There are 20 homozygotes in gnomad4_exome. There are 1785 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.67+62T>G		intron_variant		ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000380152.8	c.67+62T>G		intron_variant		5	NM_000059.4	ENSP00000369497.3
BRCA2	ENST00000530893.7	c.-303+66T>G		intron_variant		1		ENSP00000499438.2
BRCA2	ENST00000614259.2	n.67+62T>G		intron_variant		2		ENSP00000506251.1

Frequencies

GnomAD3 genomes AF: 0.00286 AC: 435 AN: 152088 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.00575

GnomAD4 exome AF: 0.00260 AC: 3419 AN: 1316910 Hom.: 20 AF XY: 0.00271 AC XY: 1785 AN XY: 659230

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.00407

Gnomad4 ASJ exome AF: 0.00793

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00460

Gnomad4 FIN exome AF: 0.00274

Gnomad4 NFE exome AF: 0.00214

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.00286 AC: 435 AN: 152206 Hom.: 2 Cov.: 33 AF XY: 0.00292 AC XY: 217 AN XY: 74406

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.00271

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00301 Hom.: 0

Bravo AF: 0.00309

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 01, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	Oct 25, 2017	- -

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	BRCA2: BP4, BS1 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Hereditary cancer-predisposing syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 11, 2015	- -
Likely benign, criteria provided, single submitter	curation	Sema4, Sema4	Mar 19, 2021	- -

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

Uncertain significance, no assertion criteria provided

clinical testing

Breast Cancer Information Core (BIC) (BRCA2)

Dec 17, 2010

- -

Hereditary breast ovarian cancer syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.63

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: rs11571574; hg19: chr13-32890726; COSMIC: COSV104659059; COSMIC: COSV104659059;