rs206119

Variant names:

• chr13-32315831-G-A
• rs206119
• NM_000059.4:c.-40+164G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-32315831-G-A
• chr13-32315831-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000059.4(BRCA2):​c.-40+164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,094 control chromosomes in the GnomAD database, including 40,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.73 (40780 hom., cov: 32)
• Consequence: BRCA2 NM_000059.4 intron
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: -0.781
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• breast-ovarian cancer, familial, susceptibility to, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• Fanconi anemia complementation group D1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P
• pancreatic cancer, susceptibility to, 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary breast ovarian cancer syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-32315831-G-A is Benign according to our data. Variant chr13-32315831-G-A is described in ClinVar as Benign. ClinVar VariationId is 209930.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRCA2	NM_000059.4	c.-40+164G>A		intron_variant	Intron 1 of 26	ENST00000380152.8	NP_000050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRCA2	ENST00000380152.8	c.-40+164G>A		intron_variant	Intron 1 of 26	5	NM_000059.4	ENSP00000369497.3
BRCA2	ENST00000530893.7	c.-405+164G>A		intron_variant	Intron 1 of 26	1		ENSP00000499438.2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110610 AN: 151978 Hom.: 40776 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.728 AC: 110656 AN: 152094 Hom.: 40780 Cov.: 32 AF XY: 0.730 AC XY: 54246 AN XY: 74358

African (AFR) AF: 0.597 AC: 24766 AN: 41488

American (AMR) AF: 0.754 AC: 11540 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2778 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4456 AN: 5148

South Asian (SAS) AF: 0.829 AC: 4002 AN: 4830

European-Finnish (FIN) AF: 0.731 AC: 7726 AN: 10572

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52831 AN: 67968

Other (OTH) AF: 0.749 AC: 1581 AN: 2112

Alfa AF: 0.763 Hom.: 63814

Bravo AF: 0.720

Asia WGS AF: 0.811 AC: 2821 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

Submissions by phenotype

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

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 0.8636 (Asian), 0.5285 (African), 0.777 (European), derived from 1000 genomes (2012-04-30). -

not provided Benign:1

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-0.78
PromoterAI		-0.17	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs206119; hg19: chr13-32889968; COSMIC: COSV61526201; COSMIC: COSV61526201;