Variant rs542551 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000059.4(BRCA2):c.9256+5252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 216,724 control chromosomes in the GnomAD database, including 6,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.22 ( 4266 hom., cov: 32)

Exomes 𝑓: 0.26 ( 2160 hom. )

Consequence

BRCA2
NM_000059.4 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:2

Conservation

PhyloP100: 2.10

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]

BRCA2 links:

IFIT1P1 (HGNC:):

IFIT1P1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 13-32385397-A-G is Benign according to our data. Variant chr13-32385397-A-G is described in ClinVar as [Benign]. Clinvar id is 209870.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32385397-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCA2	NM_000059.4 linkuse as main transcript	c.9256+5252A>G		intron_variant		ENST00000380152.8	NP_000050.3	P51587

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
BRCA2	ENST00000380152.8 linkuse as main transcript	c.9256+5252A>G	intron_variant	5	NM_000059.4	ENSP00000369497.3	P51587
BRCA2	ENST00000530893.7 linkuse as main transcript	c.8887+5252A>G	intron_variant	1		ENSP00000499438.2	A0A590UJI7
BRCA2	ENST00000614259.2 linkuse as main transcript	n.*1314+5252A>G	intron_variant	2		ENSP00000506251.1	A0A7P0TAP7

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33979

AN:

151994

Hom.:

4264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.258

AC:

16649

AN:

64614

Hom.:

2160

Cov.:

AF XY:

0.260

AC XY:

9870

AN XY:

37904

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.363

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.305

Gnomad4 FIN exome

AF:

0.212

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.223

AC:

33994

AN:

152110

Hom.:

4266

Cov.:

AF XY:

0.222

AC XY:

16535

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.289

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.251

Hom.:

660

Bravo

AF:

0.225

Asia WGS

AF:

0.257

AC:

893

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2

Benign:1

Benign, reviewed by expert panel

curation

Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

Jan 12, 2015

Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.1923 (Asian), 0.09959 (African), 0.248 (European), derived from 1000 genomes (2012-04-30). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.45

DANN

Benign

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over