15-40729927-CA-CAA

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_002875.5(RAD51):​c.855dupA​(p.Pro286ThrfsTer37) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

RAD51
NM_002875.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 8.96

Publications

1 publications found
Variant links:
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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-40729927-C-CA is Pathogenic according to our data. Variant chr15-40729927-C-CA is described in ClinVar as [Pathogenic]. Clinvar id is 29869.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAD51NM_002875.5 linkc.855dupA p.Pro286ThrfsTer37 frameshift_variant Exon 9 of 10 ENST00000267868.8 NP_002866.2 Q06609-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAD51ENST00000267868.8 linkc.855dupA p.Pro286ThrfsTer37 frameshift_variant Exon 9 of 10 1 NM_002875.5 ENSP00000267868.3 Q06609-1
RAD51ENST00000532743.6 linkc.855dupA p.Pro286ThrfsTer37 frameshift_variant Exon 9 of 10 2 ENSP00000433924.2 Q06609-1
RAD51ENST00000557850.5 linkc.564dupA p.Pro189ThrfsTer37 frameshift_variant Exon 7 of 8 2 ENSP00000454176.1 Q06609-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Mirror movements 2 Pathogenic:1Other:1
Feb 10, 2012
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

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GeneReviews
Significance:not provided
Review Status:no classification provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
9.0
Mutation Taster
=4/196
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs34091239; hg19: chr15-41022125; COSMIC: COSV51111631; COSMIC: COSV51111631; API