NM_058216.3(RAD51C):c.964del (p.Arg322fs) AND Fanconi anemia complementation group O

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 23, 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:: RCV000701832.8

Allele description [Variation Report for NM_058216.3(RAD51C):c.964del (p.Arg322fs)]

NM_058216.3(RAD51C):c.964del (p.Arg322fs)

Gene:

RAD51C:RAD51 paralog C [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q22

Genomic location:

Preferred name:

NM_058216.3(RAD51C):c.964del (p.Arg322fs)

HGVS:

NC_000017.11:g.58724099del
NG_023199.1:g.36498del
NM_058216.3:c.964delMANE SELECT
NP_478123.1:p.Arg322fs
LRG_314:g.36498del
NC_000017.10:g.56801458del
NC_000017.10:g.56801460del
NM_058216.2:c.964del
NM_058216.2:c.964delA
NR_103872.2:n.839del

Protein change:

R322fs

Links:

dbSNP: rs1555603056

NCBI 1000 Genomes Browser:

rs1555603056

Molecular consequence:

NM_058216.3:c.964del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_103872.2:n.839del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000830651	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 23, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12966089, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000830651

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 23, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV000830651.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Arg322Glyfs*42) in the RAD51C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acid(s) of the RAD51C protein. This variant is not present in population databases (gnomAD no frequency). 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: 492399). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine