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NM_058216.3(RAD51C):c.404+2T>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 5, 2023
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:
RCV000221514.6

Allele description [Variation Report for NM_058216.3(RAD51C):c.404+2T>C]

NM_058216.3(RAD51C):c.404+2T>C

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.404+2T>C
Other names:
*136Q
HGVS:
  • NC_000017.11:g.58695191T>C
  • NG_023199.1:g.7590T>C
  • NG_047169.1:g.1889A>G
  • NM_002876.4:c.406T>C
  • NM_058216.3:c.404+2T>CMANE SELECT
  • NP_002867.1:p.Ter136Gln
  • LRG_314t1:c.404+2T>C
  • LRG_314:g.7590T>C
  • NC_000017.10:g.56772552T>C
  • NM_002876.2:c.406T>C
  • NM_058216.1:c.404+2T>C
  • NM_058216.2:c.404+2T>C
  • NR_103873.1:n.374T>C
Links:
dbSNP: rs730881931
NCBI 1000 Genomes Browser:
rs730881931
Molecular consequence:
  • NR_103873.1:n.374T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_058216.3:c.404+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_002876.4:c.406T>C - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000278163Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Sep 5, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2. doi: 10.1038/gim.2016.21.

PubMed [citation]
PMID:
26681312
PMCID:
PMC4985612

Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D.

Yang X, Song H, Leslie G, Engel C, Hahnen E, Auber B, Horváth J, Kast K, Niederacher D, Turnbull C, Houlston R, Hanson H, Loveday C, Dolinsky JS, LaDuca H, Ramus SJ, Menon U, Rosenthal AN, Jacobs I, Gayther SA, Dicks E, Nevanlinna H, et al.

J Natl Cancer Inst. 2020 Dec 14;112(12):1242-1250. doi: 10.1093/jnci/djaa030.

PubMed [citation]
PMID:
32107557
PMCID:
PMC7735771

Details of each submission

From Ambry Genetics, SCV000278163.8

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

Description

The c.404+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 2 in the RAD51C gene. This alteration was identified in one patient with ovarian cancer out of 10030 consecutive patients referred for evaluation by an NGS hereditary cancer panel (Susswein LR et al. Genet. Med., 2016 08;18:823-32). In another study, this alteration was identified in two families with a history of breast and/or ovarian cancer (Yang X et al. J Natl Cancer Inst, 2020 12;112:1242-1250). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024