NM_002875.5:c.*718G>C

Variant names:

• chr15-40731896-G-C
• rs7180135
• NM_002875.5:c.*718G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002875.5(RAD51):​c.*718G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

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>C		3_prime_UTR	Exon 10 of 10	NP_002866.2
	RAD51	NM_001164269.2		c.*718G>C		3_prime_UTR	Exon 10 of 10	NP_001157741.1
	RAD51	NM_133487.4		c.*718G>C		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>C		3_prime_UTR	Exon 10 of 10	ENSP00000267868.3
	RAD51	ENST00000645673.2		c.*718G>C		3_prime_UTR	Exon 10 of 10	ENSP00000493712.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 59576 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27674

African (AFR) AF: 0.00 AC: 0 AN: 2666

American (AMR) AF: 0.00 AC: 0 AN: 1750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3758

East Asian (EAS) AF: 0.00 AC: 0 AN: 8848

South Asian (SAS) AF: 0.00 AC: 0 AN: 524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 36764

Other (OTH) AF: 0.00 AC: 0 AN: 4860

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.59
DANN	Benign	0.25
PhyloP100		-0.35

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;