13-32326656-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000059.4(BRCA2):​c.631+43G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000641 in 1,388,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00065 ( 1 hom. )

Consequence

BRCA2
NM_000059.4 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:7

Conservation

PhyloP100: -1.18
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 13-32326656-G-T is Benign according to our data. Variant chr13-32326656-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 52055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-32326656-G-T is described in Lovd as [Likely_benign]. Variant chr13-32326656-G-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRCA2NM_000059.4 linkc.631+43G>T intron_variant Intron 7 of 26 ENST00000380152.8 NP_000050.3 P51587

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRCA2ENST00000380152.8 linkc.631+43G>T intron_variant Intron 7 of 26 5 NM_000059.4 ENSP00000369497.3 P51587
BRCA2ENST00000530893.7 linkc.262+43G>T intron_variant Intron 7 of 26 1 ENSP00000499438.2 A0A590UJI7
BRCA2ENST00000614259.2 linkn.631+43G>T intron_variant Intron 6 of 25 2 ENSP00000506251.1 A0A7P0TAP7

Frequencies

GnomAD3 genomes
AF:
0.000605
AC:
92
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00126
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000465
AC:
108
AN:
232486
Hom.:
0
AF XY:
0.000485
AC XY:
61
AN XY:
125730
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000337
Gnomad ASJ exome
AF:
0.000114
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00100
Gnomad NFE exome
AF:
0.000790
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000646
AC:
798
AN:
1235984
Hom.:
1
Cov.:
18
AF XY:
0.000688
AC XY:
428
AN XY:
621980
show subpopulations
Gnomad4 AFR exome
AF:
0.000107
Gnomad4 AMR exome
AF:
0.0000250
Gnomad4 ASJ exome
AF:
0.0000418
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000720
Gnomad4 NFE exome
AF:
0.000801
Gnomad4 OTH exome
AF:
0.000399
GnomAD4 genome
AF:
0.000604
AC:
92
AN:
152268
Hom.:
0
Cov.:
33
AF XY:
0.000591
AC XY:
44
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00126
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000973
Hom.:
0
Bravo
AF:
0.000453

ClinVar

Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:1Benign:3
Dec 17, 2010
Breast Cancer Information Core (BIC) (BRCA2)
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Oct 09, 2014
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 02, 2020
BRCAlab, Lund University
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Apr 21, 2016
Michigan Medical Genetics Laboratories, University of Michigan
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:2
-
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not specified Benign:1
Mar 04, 2025
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary breast ovarian cancer syndrome Benign:1
Dec 06, 2024
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.88
CADD
Benign
0.20
DANN
Benign
0.66

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs276174869; hg19: chr13-32900793; API