NM_005732.4(RAD50):c.2525T>C (p.Val842Ala) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Dec 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000115941.17

Allele description [Variation Report for NM_005732.4(RAD50):c.2525T>C (p.Val842Ala)]

NM_005732.4(RAD50):c.2525T>C (p.Val842Ala)

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.2525T>C (p.Val842Ala)
Other names:
p.V842A:GTT>GCT
HGVS:
  • NC_000005.10:g.132604806T>C
  • NG_021151.1:g.52883T>C
  • NG_021151.2:g.52830T>C
  • NM_005732.4:c.2525T>CMANE SELECT
  • NP_005723.2:p.Val842Ala
  • LRG_312t1:c.2525T>C
  • LRG_312:g.52830T>C
  • LRG_312p1:p.Val842Ala
  • NC_000005.9:g.131940498T>C
  • NM_005732.3:c.2525T>C
  • Q92878:p.Val842Ala
  • p.V842A
Protein change:
V842A
Links:
UniProtKB: Q92878#VAR_029170; dbSNP: rs28903093
NCBI 1000 Genomes Browser:
rs28903093
Molecular consequence:
  • NM_005732.4:c.2525T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000186667Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Dec 31, 2018)
germlineclinical testing

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

Citation Link,

SCV000254889Invitaecriteria provided, single submitter
Likely benign
(Dec 7, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Evaluation of RAD50 in familial breast cancer predisposition.

Tommiska J, Seal S, Renwick A, Barfoot R, Baskcomb L, Jayatilake H, Bartkova J, Tallila J, Kaare M, Tamminen A, Heikkilä P, Evans DG, Eccles D, Aittomäki K, Blomqvist C, Bartek J, Stratton MR, Nevanlinna H, Rahman N.

Int J Cancer. 2006 Jun 1;118(11):2911-6.

PubMed [citation]
PMID:
16385572

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Ambry Genetics, SCV000186667.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.V842A variant (also known as c.2525T>C), located in coding exon 16 of the RAD50 gene, results from a T to C substitution at nucleotide position 2525. The valine at codon 842 is replaced by alanine, an amino acid with similar properties. This change occurs at the first nucleotide of coding exon 16. This variant has been detected in a familial breast cancer kindred from the United Kingdom; however, specific clinical information and co-segregation data is not available (Tommiska J et al. Int. J. Cancer. 2006 Jun;118:2911-6). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Invitae, SCV000254889.9

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

Last Updated: Jun 14, 2021

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