Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

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

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 27, 2020
Accession:
VCV000128001.9
Variation ID:
128001
Description:
single nucleotide variant
Help

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

Allele ID
133458
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
5q31.1
Genomic location
5: 132595780 (GRCh38) GRCh38 UCSC
5: 131931472 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000005.10:g.132595780G>A
NC_000005.9:g.131931472G>A
NG_021151.1:g.43857G>A
... more HGVS
Protein change
R726H
Other names
p.R726H:CGT>CAT
Canonical SPDI
NC_000005.10:132595779:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (A)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00016
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD), exomes 0.00014
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
The Genome Aggregation Database (gnomAD) 0.00025
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00026
Trans-Omics for Precision Medicine (TOPMed) 0.00031
Links
ClinGen: CA331865
dbSNP: rs28903092
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Feb 27, 2014 RCV000212914.1
Uncertain significance 1 criteria provided, single submitter May 23, 2017 RCV000515380.1
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Oct 27, 2020 RCV000115937.17
Uncertain significance 1 no assertion criteria provided Jan 11, 2018 RCV000766182.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
RAD50 - - GRCh38
GRCh37
2185 2611

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Feb 27, 2014)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000149846.12
Submitted: (Jan 29, 2019)
Evidence details
Comment:
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 … (more)
Likely benign
(Mar 24, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000184077.6
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (2)
Comment:
In silico models in agreement (benign);Insufficient or conflicting evidence;No disease association in small case-control study;Seen in trans with a mutation or in homozygous state in … (more)
Uncertain significance
(Oct 27, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Invitae
Accession: SCV000261760.9
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces arginine with histidine at codon 726 of the RAD50 protein (p.Arg726His). The arginine residue is moderately conserved and there is a … (more)
Uncertain significance
(May 23, 2017)
criteria provided, single submitter
Method: clinical testing
Nijmegen breakage syndrome-like disorder
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000611512.1
Submitted: (May 23, 2017)
Evidence details
Uncertain significance
(Aug 01, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
GeneKor MSA
Accession: SCV000822148.1
Submitted: (Aug 08, 2018)
Evidence details
Uncertain significance
(Jan 11, 2018)
no assertion criteria provided
Method: research
Premature ovarian insufficiency
Allele origin: germline
Reproductive Development, Murdoch Childrens Research Institute
Accession: SCV000882516.1
Submitted: (Oct 06, 2018)
Evidence details

Functional evidence

Help
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Help
Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer. Maxwell KN Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25503501
Evaluation of RAD50 in familial breast cancer predisposition. Tommiska J International journal of cancer 2006 PMID: 16385572

Text-mined citations for rs28903092...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021