rs1060502605
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_058216.3(RAD51C):c.851_854delATCA(p.Asn284ArgfsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_058216.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:2
The c.851_854delATCA pathogenic mutation, located in coding exon 6 of the RAD51C gene, results from a deletion of 4 nucleotides at nucleotide positions 851 to 854, causing a translational frameshift with a predicted alternate stop codon (p.N284Rfs*2). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
This variant deletes 4 nucleotides in exon 6 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast and/or ovarian cancer (PMID: 26534844). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. -
Breast-ovarian cancer, familial, susceptibility to, 3 Pathogenic:2
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This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. -
Fanconi anemia complementation group O Pathogenic:1
While this particular variant has not been reported in the literature, truncating variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917). For these reasons, this variant has been classified as Pathogenic. This sequence change deletes 4 nucleotides from exon 6 of the RAD51C mRNA (c.851_854delATCA), causing a frameshift at codon 284. This creates a premature translational stop signal (p.Asn284Argfs*2) and is expected to result in an absent or disrupted protein product. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at