NM_005732.4(RAD50):c.2840T>C (p.Ile947Thr) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Feb 14, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001194193.1

Allele description [Variation Report for NM_005732.4(RAD50):c.2840T>C (p.Ile947Thr)]

NM_005732.4(RAD50):c.2840T>C (p.Ile947Thr)

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.2840T>C (p.Ile947Thr)
Other names:
p.I947T:ATT>ACT
HGVS:
  • NC_000005.10:g.132609127T>C
  • NG_021151.1:g.57204T>C
  • NG_021151.2:g.57151T>C
  • NM_005732.4:c.2840T>CMANE SELECT
  • NP_005723.2:p.Ile947Thr
  • LRG_312t1:c.2840T>C
  • LRG_312:g.57151T>C
  • LRG_312p1:p.Ile947Thr
  • NC_000005.9:g.131944819T>C
  • NM_005732.3:c.2840T>C
  • p.I947T
Protein change:
I947T
Links:
dbSNP: rs150401251
NCBI 1000 Genomes Browser:
rs150401251
Molecular consequence:
  • NM_005732.4:c.2840T>C - 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
SCV001363538Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Feb 14, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Patterns and functional implications of rare germline variants across 12 cancer types.

Lu C, Xie M, Wendl MC, Wang J, McLellan MD, Leiserson MD, Huang KL, Wyczalkowski MA, Jayasinghe R, Banerjee T, Ning J, Tripathi P, Zhang Q, Niu B, Ye K, Schmidt HK, Fulton RS, McMichael JF, Batra P, Kandoth C, Bharadwaj M, Koboldt DC, et al.

Nat Commun. 2015 Dec 22;6:10086. doi: 10.1038/ncomms10086.

PubMed [citation]
PMID:
26689913
PMCID:
PMC4703835

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363538.1

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

Description

Variant summary: RAD50 c.2840T>C (p.Ile947Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.6e-05 in 274800 control chromosomes, predominantly within the Non-Finnish European subpopulation at a frequency of 0.00014 in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in RAD50 causing Hereditary Breast and Ovarian Cancer phenotype (6.3e-05), suggesting that the variant might be a benign polymorphism found primarily in populations of Non-Finnish European origin. c.2840T>C has been reported in the literature in an individual affected with lung adenocarcinoma (Lu 2015). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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

Last Updated: Oct 8, 2021

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