15-40731896-G-A

Variant names:

• chr15-40731896-G-A
• rs7180135
• NM_002875.5:c.*718G>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.*718G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 211,414 control chromosomes in the GnomAD database, including 44,986 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 0.64 (32142 hom., cov: 31)
  • Exomes 𝑓: 0.64 (12844 hom.)
• Consequence: RAD51 NM_002875.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 39 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51	NM_002875.5	MANE Select	c.*718G>A		3_prime_UTR	Exon 10 of 10	NP_002866.2
	RAD51	NM_001164269.2		c.*718G>A		3_prime_UTR	Exon 10 of 10	NP_001157741.1
	RAD51	NM_133487.4		c.*718G>A		3_prime_UTR	Exon 10 of 10	NP_597994.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51	ENST00000267868.8	TSL:1 MANE Select	c.*718G>A		3_prime_UTR	Exon 10 of 10	ENSP00000267868.3
	RAD51	ENST00000645673.2		c.*718G>A		3_prime_UTR	Exon 10 of 10	ENSP00000493712.2

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97758 AN: 151882 Hom.: 32086 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.642 AC: 38163 AN: 59414 Hom.: 12844 Cov.: 0 AF XY: 0.641 AC XY: 17677 AN XY: 27588

African (AFR) AF: 0.698 AC: 1859 AN: 2662

American (AMR) AF: 0.705 AC: 1228 AN: 1742

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2263 AN: 3750

East Asian (EAS) AF: 0.959 AC: 8484 AN: 8844

South Asian (SAS) AF: 0.760 AC: 398 AN: 524

European-Finnish (FIN) AF: 0.556 AC: 20 AN: 36

Middle Eastern (MID) AF: 0.576 AC: 212 AN: 368

European-Non Finnish (NFE) AF: 0.564 AC: 20654 AN: 36642

Other (OTH) AF: 0.628 AC: 3045 AN: 4846

GnomAD4 genome AF: 0.644 AC: 97877 AN: 152000 Hom.: 32142 Cov.: 31 AF XY: 0.654 AC XY: 48557 AN XY: 74286

African (AFR) AF: 0.690 AC: 28566 AN: 41416

American (AMR) AF: 0.683 AC: 10428 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2110 AN: 3464

East Asian (EAS) AF: 0.925 AC: 4789 AN: 5176

South Asian (SAS) AF: 0.772 AC: 3726 AN: 4826

European-Finnish (FIN) AF: 0.690 AC: 7290 AN: 10558

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38899 AN: 67982

Other (OTH) AF: 0.619 AC: 1305 AN: 2108

Alfa AF: 0.623 Hom.: 3848

Bravo AF: 0.648

Asia WGS AF: 0.845 AC: 2938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.24
PhyloP100		-0.35
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: rs7180135; hg19: chr15-41024094;