rs2304579

Variant names:

• chr15-40698955-A-G
• rs2304579
• NM_002875.5:c.87+110A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40698955-A-G
• chr15-40698955-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002875.5(RAD51):​c.87+110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 1,081,130 control chromosomes in the GnomAD database, including 3,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (629 hom., cov: 32)
  • Exomes 𝑓: 0.076 (3104 hom.)
• Consequence: RAD51 NM_002875.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.399
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-40698955-A-G is Benign according to our data. Variant chr15-40698955-A-G is described in ClinVar as Benign. ClinVar VariationId is 1271457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51	NM_002875.5	c.87+110A>G		intron_variant	Intron 2 of 9	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8	c.87+110A>G		intron_variant	Intron 2 of 9	1	NM_002875.5	ENSP00000267868.3
RAD51	ENST00000532743.6	c.87+110A>G		intron_variant	Intron 2 of 9	2		ENSP00000433924.2
RAD51	ENST00000557850.5	c.87+110A>G		intron_variant	Intron 2 of 7	2		ENSP00000454176.1

Frequencies

GnomAD3 genomes AF: 0.0890 AC: 13541 AN: 152074 Hom.: 625 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0821

GnomAD4 exome AF: 0.0763 AC: 70903 AN: 928938 Hom.: 3104 AF XY: 0.0786 AC XY: 37723 AN XY: 480100

African (AFR) AF: 0.122 AC: 2724 AN: 22250

American (AMR) AF: 0.0687 AC: 2613 AN: 38026

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 969 AN: 22366

East Asian (EAS) AF: 0.109 AC: 3820 AN: 34946

South Asian (SAS) AF: 0.121 AC: 8711 AN: 72100

European-Finnish (FIN) AF: 0.0870 AC: 4095 AN: 47070

Middle Eastern (MID) AF: 0.108 AC: 502 AN: 4648

European-Non Finnish (NFE) AF: 0.0683 AC: 44032 AN: 644782

Other (OTH) AF: 0.0804 AC: 3437 AN: 42750

GnomAD4 genome AF: 0.0891 AC: 13555 AN: 152192 Hom.: 629 Cov.: 32 AF XY: 0.0897 AC XY: 6674 AN XY: 74404

African (AFR) AF: 0.116 AC: 4811 AN: 41526

American (AMR) AF: 0.0639 AC: 977 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.128 AC: 662 AN: 5190

South Asian (SAS) AF: 0.120 AC: 579 AN: 4828

European-Finnish (FIN) AF: 0.0924 AC: 978 AN: 10584

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0741 AC: 5040 AN: 67994

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.0669 Hom.: 134

Bravo AF: 0.0886

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.79
PhyloP100		-0.40
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: rs2304579; hg19: chr15-40991153; COSMIC: COSV51111302; COSMIC: COSV51111302;