chr15-40696823-T-C

Variant names:

• chr15-40696823-T-C
• rs2619681
• NM_002875.5:c.-3+1398T>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.-3+1398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,134 control chromosomes in the GnomAD database, including 47,198 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 0.78 (47198 hom., cov: 33)
• Consequence: RAD51 NM_002875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 18 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51	NM_002875.5	c.-3+1398T>C		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+1398T>C		intron_variant	Intron 1 of 9	1	NM_002875.5	ENSP00000267868.3
RAD51	ENST00000532743.6	c.-3+1197T>C		intron_variant	Intron 1 of 9	2		ENSP00000433924.2
RAD51	ENST00000557850.5	c.-3+1398T>C		intron_variant	Intron 1 of 7	2		ENSP00000454176.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118455 AN: 152014 Hom.: 47158 Cov.: 33

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.779 AC: 118537 AN: 152134 Hom.: 47198 Cov.: 33 AF XY: 0.773 AC XY: 57516 AN XY: 74394

African (AFR) AF: 0.763 AC: 31666 AN: 41484

American (AMR) AF: 0.652 AC: 9944 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2748 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1699 AN: 5180

South Asian (SAS) AF: 0.693 AC: 3351 AN: 4834

European-Finnish (FIN) AF: 0.847 AC: 8963 AN: 10580

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57593 AN: 68012

Other (OTH) AF: 0.774 AC: 1638 AN: 2116

Alfa AF: 0.815 Hom.: 82571

Bravo AF: 0.756

Asia WGS AF: 0.539 AC: 1874 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.48
PhyloP100		-0.27
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: rs2619681; hg19: chr15-40989021;