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NM_058216.3(RAD51C):c.1005C>A (p.Cys335Ter) AND Fanconi anemia complementation group O

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 7, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000232127.13

Allele description [Variation Report for NM_058216.3(RAD51C):c.1005C>A (p.Cys335Ter)]

NM_058216.3(RAD51C):c.1005C>A (p.Cys335Ter)

Gene:
RAD51C:RAD51 paralog C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q22
Genomic location:
Preferred name:
NM_058216.3(RAD51C):c.1005C>A (p.Cys335Ter)
HGVS:
  • NC_000017.11:g.58732523C>A
  • NG_023199.1:g.44922C>A
  • NM_058216.3:c.1005C>AMANE SELECT
  • NP_478123.1:p.Cys335Ter
  • LRG_314t1:c.1005C>A
  • LRG_314:g.44922C>A
  • NC_000017.10:g.56809884C>A
  • NM_058216.1:c.1005C>A
  • NM_058216.2:c.1005C>A
  • NR_103872.2:n.880C>A
Protein change:
C335*
Links:
dbSNP: rs759292615
NCBI 1000 Genomes Browser:
rs759292615
Molecular consequence:
  • NR_103872.2:n.880C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_058216.3:c.1005C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Fanconi anemia complementation group O
Identifiers:
MONDO: MONDO:0013248; MedGen: C3150653; Orphanet: 84; OMIM: 613390

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000291208Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Mar 7, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of functional domains in the RAD51L2 (RAD51C) protein and its requirement for gene conversion.

French CA, Tambini CE, Thacker J.

J Biol Chem. 2003 Nov 14;278(46):45445-50. Epub 2003 Sep 8.

PubMed [citation]
PMID:
12966089

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000291208.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Cys335*) in the RAD51C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the RAD51C protein. This variant is present in population databases (rs759292615, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 231450). This variant disrupts the nuclear localization signal (NLS) of the RAD51C protein, which is important for proper localization and function of the RAD51C protein (PMID:12966089). While functional studies have not been performed to directly test the effect of this variant on RAD51C protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025