NM_058216.3(RAD51C):c.1005C>A (p.Cys335Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 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:: RCV000220031.6

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:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000275300	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Apr 23, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12442171, 29054568 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000275300

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Apr 23, 2024)

germline

clinical testing

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

Citation Link

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

Insights into DNA recombination from the structure of a RAD51-BRCA2 complex.

Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, Venkitaraman AR.

Nature. 2002 Nov 21;420(6913):287-93. Epub 2002 Nov 10.

PubMed [citation]

PMID:: 12442171

Genetic epidemiology of ovarian cancer and prospects for polygenic risk prediction.

Jones MR, Kamara D, Karlan BY, Pharoah PDP, Gayther SA.

Gynecol Oncol. 2017 Dec;147(3):705-713. doi: 10.1016/j.ygyno.2017.10.001. Epub 2017 Oct 18. Review.

PubMed [citation]

PMID:: 29054568

Details of each submission

From Ambry Genetics, SCV000275300.8

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

Description

The p.C335* variant (also known as c.1005C>A), located in coding exon 8 of the RAD51C gene, results from a C to A substitution at nucleotide position 1005. This changes the amino acid from a cysteine to a stop codon within coding exon 8. This alteration occurs at the 3' terminus of RAD51C gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 11% of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be 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

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