NM_005732.4(RAD50):c.2177G>A (p.Arg726His) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Feb 27, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000212914.1

Allele description [Variation Report for NM_005732.4(RAD50):c.2177G>A (p.Arg726His)]

NM_005732.4(RAD50):c.2177G>A (p.Arg726His)

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.2177G>A (p.Arg726His)
Other names:
p.R726H:CGT>CAT
HGVS:
  • NC_000005.10:g.132595780G>A
  • NG_021151.1:g.43857G>A
  • NG_021151.2:g.43804G>A
  • NM_005732.4:c.2177G>AMANE SELECT
  • NP_005723.2:p.Arg726His
  • LRG_312t1:c.2177G>A
  • LRG_312:g.43804G>A
  • LRG_312p1:p.Arg726His
  • NC_000005.9:g.131931472G>A
  • NM_005732.3:c.2177G>A
  • p.R726H
Protein change:
R726H
Links:
dbSNP: rs28903092
NCBI 1000 Genomes Browser:
rs28903092
Molecular consequence:
  • NM_005732.4:c.2177G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000149846GeneDxcriteria provided, single submitter
Uncertain significance
(Feb 27, 2014)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000149846.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

RAD50 has been only recently described in association with cancer predisposition and the risks are not well understood. This variant is denoted RAD50 c.2177G>A at the cDNA level, p.Arg726His (R726H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant was observed in one individual with familial breast cancer (Tommiska 2006). RAD50 Arg726His was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a conservative substitution of one positive polar amino acid for another, altering a position that is well conserved throughout evolution and is located in the Zinc-hook domain via UniProt. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. At a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the RAD50 gene, remain unclear. Of note, two deleterious RAD50 mutations on opposite chromosomes (in trans) have been reported to cause Nijmegen breakage-like disorder (Waltes 2009). Therefore, if these variants are in trans, and if this patient does not have a related congenital disorder, then at least one is likely benign. Parental or family testing could help determine whether the variants are in cis or trans.

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

Last Updated: Nov 27, 2021

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