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NM_058216.3(RAD51C):c.774del (p.Thr259fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 13, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000581899.8

Allele description [Variation Report for NM_058216.3(RAD51C):c.774del (p.Thr259fs)]

NM_058216.3(RAD51C):c.774del (p.Thr259fs)

Gene:
RAD51C:RAD51 paralog C [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17q22
Genomic location:
Preferred name:
NM_058216.3(RAD51C):c.774del (p.Thr259fs)
HGVS:
  • NC_000017.11:g.58709927del
  • NG_023199.1:g.22326del
  • NM_058216.3:c.774delMANE SELECT
  • NP_478123.1:p.Thr259fs
  • LRG_314t1:c.774del
  • LRG_314:g.22326del
  • NC_000017.10:g.56787288del
  • NM_058216.1:c.774del
  • NM_058216.1:c.774delT
  • NM_058216.2:c.774del
  • NM_058216.2:c.774delT
  • NM_058216.3:c.774delTMANE SELECT
  • NR_103872.2:n.649del
Protein change:
T259fs
Links:
dbSNP: rs754367349
NCBI 1000 Genomes Browser:
rs754367349
Molecular consequence:
  • NM_058216.3:c.774del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_103872.2:n.649del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000691266Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Sep 29, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001189230Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Pathogenic
(Jan 13, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families.

Romero A, Pérez-Segura P, Tosar A, García-Saenz JA, Díaz-Rubio E, Caldés T, de la Hoya M.

Breast Cancer Res Treat. 2011 Oct;129(3):939-46. doi: 10.1007/s10549-011-1543-x. Epub 2011 May 3.

PubMed [citation]
PMID:
21537932
See all PubMed Citations (5)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000691266.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Ambry Genetics, SCV001189230.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The c.774delT pathogenic mutation, located in coding exon 5 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 774, causing a translational frameshift with a predicted alternate stop codon (p.T259Lfs*4). This mutation has been reported in multiple individuals with a personal and/or family history of breast and/or ovarian cancer and has also been proposed as a Swedish founder mutation (Romero A et al. Breast Cancer Res. Treat. 2011 Oct;129:939-46; Vuorela M et al. Breast Cancer Res. Treat. 2011 Dec;130:1003-10; Osorio A et al. Hum. Mol. Genet., 2012 Jul;21:2889-98; Song H et al. J. Clin. Oncol. 2015 Sep;33:2901-7). In addition to the clinical data presented in the literature, 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.

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

Last Updated: May 1, 2024