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NM_005732.4(RAD50):c.3755T>A (p.Ile1252Lys) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 24, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001870630.3

Allele description

NM_005732.4(RAD50):c.3755T>A (p.Ile1252Lys)

Genes:
RAD50:RAD50 double strand break repair protein [Gene - OMIM - HGNC]
TH2LCRR:T helper type 2 locus control region associated RNA [Gene - HGNC]
TH2-LCR:Th2 cytokine locus control region [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.1
Genomic location:
Preferred name:
NM_005732.4(RAD50):c.3755T>A (p.Ile1252Lys)
HGVS:
  • NC_000005.10:g.132642180T>A
  • NG_021151.2:g.90204T>A
  • NG_042308.1:g.13018T>A
  • NM_005732.4:c.3755T>AMANE SELECT
  • NP_005723.2:p.Ile1252Lys
  • LRG_312t1:c.3755T>A
  • LRG_312:g.90204T>A
  • LRG_312p1:p.Ile1252Lys
  • NC_000005.9:g.131977872T>A
Protein change:
I1252K
Links:
dbSNP: rs2149866803
NCBI 1000 Genomes Browser:
rs2149866803
Molecular consequence:
  • NM_005732.4:c.3755T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002134032Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 24, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV002134032.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with lysine at codon 1252 of the RAD50 protein (p.Ile1252Lys). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and lysine.

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

Last Updated: Feb 28, 2024