15-40696220-C-A

Variant names:

• chr15-40696220-C-A
• rs2619680
• NM_002875.5:c.-3+795C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

RAD51 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group R

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mirror movements 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial congenital mirror movements

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAD51	NM_002875.5	c.-3+795C>A		intron_variant	Intron 1 of 9	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8	c.-3+795C>A		intron_variant	Intron 1 of 9	1	NM_002875.5	ENSP00000267868.3
RAD51	ENST00000532743.6	c.-3+594C>A		intron_variant	Intron 1 of 9	2		ENSP00000433924.2
RAD51	ENST00000557850.5	c.-3+795C>A		intron_variant	Intron 1 of 7	2		ENSP00000454176.1

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

African (AFR) AF: 0.647 AC: 26800 AN: 41414

American (AMR) AF: 0.398 AC: 6072 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1504 AN: 3464

East Asian (EAS) AF: 0.228 AC: 1178 AN: 5178

South Asian (SAS) AF: 0.351 AC: 1689 AN: 4814

European-Finnish (FIN) AF: 0.403 AC: 4228 AN: 10504

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33732 AN: 67968

Other (OTH) AF: 0.501 AC: 1058 AN: 2112

Alfa AF: 0.429 Hom.: 2363

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
PhyloP100		-0.84
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: rs2619680; hg19: chr15-40988418;