15-40731680-T-G

Variant names:

• chr15-40731680-T-G
• rs12593359
• NM_002875.5:c.*502T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002875.5(RAD51):​c.*502T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 239,908 control chromosomes in the GnomAD database, including 34,095 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 0.50 (19574 hom., cov: 32)
  • Exomes 𝑓: 0.56 (14521 hom.)
• Consequence: RAD51 NM_002875.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590
• Publications: 34 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51	NM_002875.5	c.*502T>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8	c.*502T>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_002875.5	ENSP00000267868.3
RAD51	ENST00000532743.6	c.*502T>G		downstream_gene_variant		2		ENSP00000433924.2
RAD51	ENST00000557850.5	c.*502T>G		downstream_gene_variant		2		ENSP00000454176.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75292 AN: 151854 Hom.: 19561 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.560 AC: 49207 AN: 87936 Hom.: 14521 Cov.: 0 AF XY: 0.561 AC XY: 23470 AN XY: 41826

African (AFR) AF: 0.380 AC: 1381 AN: 3630

American (AMR) AF: 0.654 AC: 3295 AN: 5042

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 2717 AN: 4756

East Asian (EAS) AF: 0.849 AC: 9877 AN: 11632

South Asian (SAS) AF: 0.663 AC: 1934 AN: 2918

European-Finnish (FIN) AF: 0.575 AC: 154 AN: 268

Middle Eastern (MID) AF: 0.469 AC: 225 AN: 480

European-Non Finnish (NFE) AF: 0.497 AC: 26109 AN: 52568

Other (OTH) AF: 0.529 AC: 3515 AN: 6642

GnomAD4 genome AF: 0.496 AC: 75329 AN: 151972 Hom.: 19574 Cov.: 32 AF XY: 0.507 AC XY: 37662 AN XY: 74286

African (AFR) AF: 0.364 AC: 15106 AN: 41446

American (AMR) AF: 0.607 AC: 9274 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1963 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4101 AN: 5166

South Asian (SAS) AF: 0.649 AC: 3126 AN: 4814

European-Finnish (FIN) AF: 0.599 AC: 6319 AN: 10550

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33826 AN: 67950

Other (OTH) AF: 0.497 AC: 1049 AN: 2110

Alfa AF: 0.474 Hom.: 7851

Bravo AF: 0.494

Asia WGS AF: 0.716 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.82
PhyloP100		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs12593359; hg19: chr15-41023878;