NM_005732.4(RAD50):c.561dup (p.Ala188fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 9, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000226081.8

Allele description [Variation Report for NM_005732.4(RAD50):c.561dup (p.Ala188fs)]

NM_005732.4(RAD50):c.561dup (p.Ala188fs)

Gene:
RAD50:RAD50 double strand break repair protein [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
5q31.1
Genomic location:
Preferred name:
NM_005732.4(RAD50):c.561dup (p.Ala188fs)
HGVS:
  • NC_000005.10:g.132579871dup
  • NG_021151.1:g.27948dup
  • NG_021151.2:g.27895dup
  • NM_005732.4:c.561dupMANE SELECT
  • NP_005723.2:p.Ala188fs
  • LRG_312t1:c.561dup
  • LRG_312:g.27895dup
  • LRG_312p1:p.Ala188fs
  • NC_000005.9:g.131915560_131915561insA
  • NC_000005.9:g.131915563dup
  • NM_005732.3:c.561dup
  • NM_005732.3:c.561dupA
Protein change:
A188fs
Links:
dbSNP: rs876659005
NCBI 1000 Genomes Browser:
rs876659005
Molecular consequence:
  • NM_005732.4:c.561dup - frameshift variant - [Sequence Ontology: SO:0001589]
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
SCV000274945Ambry Geneticscriteria provided, single submitter
Pathogenic
(Mar 19, 2019)
germlineclinical testing

Citation Link,

SCV000289074Invitaecriteria provided, single submitter
Pathogenic
(Sep 9, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder.

Waltes R, Kalb R, Gatei M, Kijas AW, Stumm M, Sobeck A, Wieland B, Varon R, Lerenthal Y, Lavin MF, Schindler D, Dörk T.

Am J Hum Genet. 2009 May;84(5):605-16. doi: 10.1016/j.ajhg.2009.04.010. Epub 2009 Apr 30.

PubMed [citation]
PMID:
19409520
PMCID:
PMC2681000
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000274945.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.561dupA pathogenic mutation, located in coding exon 5 of the RAD50 gene, results from a duplication of A at nucleotide position 561, causing a translational frameshift with a predicted alternate stop codon (p.A188Sfs*30). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

From Invitae, SCV000289074.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Ala188Serfs*30) in the RAD50 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 231180). Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 16385572, 19409520). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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