NM_005732.4(RAD50):c.2173C>T (p.Arg725Trp) AND not specified

Clinical significance:Likely benign (Last evaluated: Jan 2, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000780661.1

Allele description [Variation Report for NM_005732.4(RAD50):c.2173C>T (p.Arg725Trp)]

NM_005732.4(RAD50):c.2173C>T (p.Arg725Trp)

Gene:
RAD50:RAD50 double strand break repair protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.1
Genomic location:
Preferred name:
NM_005732.4(RAD50):c.2173C>T (p.Arg725Trp)
HGVS:
  • NC_000005.10:g.132595776C>T
  • NG_021151.1:g.43853C>T
  • NG_021151.2:g.43800C>T
  • NM_005732.4:c.2173C>TMANE SELECT
  • NP_005723.2:p.Arg725Trp
  • LRG_312t1:c.2173C>T
  • LRG_312:g.43800C>T
  • LRG_312p1:p.Arg725Trp
  • NC_000005.9:g.131931468C>T
  • NM_005732.3:c.2173C>T
  • p.R725W
Protein change:
R725W
Links:
dbSNP: rs369560280
NCBI 1000 Genomes Browser:
rs369560280
Molecular consequence:
  • NM_005732.4:c.2173C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000918119Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Jan 2, 2018)
germlineclinical testing

PubMed (2)
[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

Rare key functional domain missense substitutions in MRE11A, RAD50, and NBN contribute to breast cancer susceptibility: results from a Breast Cancer Family Registry case-control mutation-screening study.

Damiola F, Pertesi M, Oliver J, Le Calvez-Kelm F, Voegele C, Young EL, Robinot N, Forey N, Durand G, Vallée MP, Tao K, Roane TC, Williams GJ, Hopper JL, Southey MC, Andrulis IL, John EM, Goldgar DE, Lesueur F, Tavtigian SV.

Breast Cancer Res. 2014 Jun 3;16(3):R58. doi: 10.1186/bcr3669.

PubMed [citation]
PMID:
24894818
PMCID:
PMC4229874

Multigene testing of moderate-risk genes: be mindful of the missense.

Young EL, Feng BJ, Stark AW, Damiola F, Durand G, Forey N, Francy TC, Gammon A, Kohlmann WK, Kaphingst KA, McKay-Chopin S, Nguyen-Dumont T, Oliver J, Paquette AM, Pertesi M, Robinot N, Rosenthal JS, Vallee M, Voegele C, Hopper JL, Southey MC, Andrulis IL, et al.

J Med Genet. 2016 Jun;53(6):366-76. doi: 10.1136/jmedgenet-2015-103398. Epub 2016 Jan 19.

PubMed [citation]
PMID:
26787654
PMCID:
PMC4893078

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918119.1

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

Description

Variant summary: The RAD50 c.2173C>T (p.Arg725Trp) variant involves the alteration of a conserved nucleotide that is located in the RAD50, zinc hook domain (InterPro). 3/3 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 55/275042 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.001541 (53/34384). This frequency is about 25 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant has been cited in the literature, though it is unclear whether it was identified in breast cancer cases or control individuals (Damiola_2014; Young_2016). Two clinical diagnostic laboratories/reputable databases classified this variant as one of uncertain significance. Taken together, this variant is classified as likely benign.

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

Last Updated: Jun 14, 2021

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