rs2619680

Positions:

• chr15-40696220-C-A
• chr15-40696220-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002875.5(RAD51):​c.-3+795C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,918 control chromosomes in the GnomAD database, including 20,395 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20395 hom., cov: 31)
• Consequence: RAD51 NM_002875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51	NM_002875.5	c.-3+795C>A		intron_variant		ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8	c.-3+795C>A		intron_variant		1	NM_002875.5	ENSP00000267868	P1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76825 AN: 151800 Hom.: 20361 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.506 AC: 76900 AN: 151918 Hom.: 20395 Cov.: 31 AF XY: 0.496 AC XY: 36791 AN XY: 74224

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.501

Alfa AF: 0.421 Hom.: 2193

Bravo AF: 0.509

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.48

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: rs2619680; hg19: chr15-40988418;