rs2304579

chr15-40698955-A-Gchr15-40698955-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002875.5(RAD51):c.87+110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 1,081,130 control chromosomes in the GnomAD database, including 3,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (629 hom., cov: 32)
  • Exomes 𝑓: 0.076 (3104 hom.)
• Consequence: RAD51 NM_002875.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.399

Genes affected

RAD51 (HGNC:9817): (RAD51 recombinase) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-40698955-A-G is Benign according to our data. Variant chr15-40698955-A-G is described in ClinVar as [Benign]. Clinvar id is 1271457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51	NM_002875.5	c.87+110A>G		intron_variant		ENST00000267868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51	ENST00000267868.8	c.87+110A>G		intron_variant		1	NM_002875.5	P1

Frequencies

GnomAD3 genomes AF: 0.0890 AC: 13541 AN: 152074 Hom.: 625 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0821

GnomAD4 exome AF: 0.0763 AC: 70903 AN: 928938 Hom.: 3104 AF XY: 0.0786 AC XY: 37723 AN XY: 480100

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0687

Gnomad4 ASJ exome AF: 0.0433

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0870

Gnomad4 NFE exome AF: 0.0683

Gnomad4 OTH exome AF: 0.0804

GnomAD4 genome AF: 0.0891 AC: 13555 AN: 152192 Hom.: 629 Cov.: 32 AF XY: 0.0897 AC XY: 6674 AN XY: 74404

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0639

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.0822

Alfa AF: 0.0551 Hom.: 65

Bravo AF: 0.0886

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.6
Dann	Benign	0.79

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: rs2304579; hg19: chr15-40991153; COSMIC: COSV51111302; COSMIC: COSV51111302;