15-40732105-T-C

Variant names:

• chr15-40732105-T-C
• rs11855560
• NM_002875.5:c.*927T>C

Variant summary

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

The NM_002875.5(RAD51):​c.*927T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 200,692 control chromosomes in the GnomAD database, including 27,437 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 (19566 hom., cov: 32)
  • Exomes 𝑓: 0.55 (7871 hom.)
• Consequence: RAD51 NM_002875.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 17 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51	NM_002875.5	c.*927T>C		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.*927T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_002875.5	ENSP00000267868.3
RAD51	ENST00000645673.2	c.*927T>C		3_prime_UTR_variant	Exon 10 of 10			ENSP00000493712.2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75255 AN: 151868 Hom.: 19553 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.552 AC: 26873 AN: 48706 Hom.: 7871 Cov.: 0 AF XY: 0.552 AC XY: 12474 AN XY: 22584

African (AFR) AF: 0.365 AC: 740 AN: 2028

American (AMR) AF: 0.646 AC: 862 AN: 1334

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1738 AN: 3112

East Asian (EAS) AF: 0.847 AC: 6635 AN: 7834

South Asian (SAS) AF: 0.653 AC: 265 AN: 406

European-Finnish (FIN) AF: 0.500 AC: 15 AN: 30

Middle Eastern (MID) AF: 0.484 AC: 151 AN: 312

European-Non Finnish (NFE) AF: 0.485 AC: 14359 AN: 29598

Other (OTH) AF: 0.520 AC: 2108 AN: 4052

GnomAD4 genome AF: 0.495 AC: 75292 AN: 151986 Hom.: 19566 Cov.: 32 AF XY: 0.507 AC XY: 37633 AN XY: 74280

African (AFR) AF: 0.364 AC: 15083 AN: 41438

American (AMR) AF: 0.608 AC: 9275 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1962 AN: 3468

East Asian (EAS) AF: 0.793 AC: 4101 AN: 5170

South Asian (SAS) AF: 0.650 AC: 3124 AN: 4808

European-Finnish (FIN) AF: 0.598 AC: 6309 AN: 10552

Middle Eastern (MID) AF: 0.531 AC: 154 AN: 290

European-Non Finnish (NFE) AF: 0.498 AC: 33829 AN: 67988

Other (OTH) AF: 0.497 AC: 1045 AN: 2104

Alfa AF: 0.490 Hom.: 2803

Bravo AF: 0.493

Asia WGS AF: 0.716 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.74
PhyloP100		1.9
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: rs11855560; hg19: chr15-41024303;