NM_000051.4(ATM):c.2074C>T (p.Arg692Cys) AND Ataxia-telangiectasia syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 19, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000051.4(ATM):c.2074C>T (p.Arg692Cys)]

NM_000051.4(ATM):c.2074C>T (p.Arg692Cys)

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000051.4(ATM):c.2074C>T (p.Arg692Cys)
  • NC_000011.10:g.108253989C>T
  • NG_009830.1:g.36158C>T
  • NM_000051.3:c.2074C>T
  • NM_000051.4:c.2074C>TMANE SELECT
  • NM_001351834.2:c.2074C>T
  • NP_000042.3:p.Arg692Cys
  • NP_000042.3:p.Arg692Cys
  • NP_001338763.1:p.Arg692Cys
  • LRG_135t1:c.2074C>T
  • LRG_135:g.36158C>T
  • LRG_135p1:p.Arg692Cys
  • NC_000011.9:g.108124716C>T
  • p.R692C
Protein change:
dbSNP: rs765965513
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000051.3:c.2074C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000051.4:c.2074C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.2074C>T - missense variant - [Sequence Ontology: SO:0001583]


Ataxia-telangiectasia syndrome (AT)
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000218725Invitaecriteria provided, single submitter
Uncertain significance
(Oct 19, 2020)
germlineclinical testing

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

Summary from all submissions

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



Rare germline variants in ATM are associated with chronic lymphocytic leukemia.

Tiao G, Improgo MR, Kasar S, Poh W, Kamburov A, Landau DA, Tausch E, Taylor-Weiner A, Cibulskis C, Bahl S, Fernandes SM, Hoang K, Rheinbay E, Kim HT, Bahlo J, Robrecht S, Fischer K, Hallek M, Gabriel S, Lander ES, Stilgenbauer S, Wu CJ, et al.

Leukemia. 2017 Oct;31(10):2244-2247. doi: 10.1038/leu.2017.201. Epub 2017 Jun 27. No abstract available.

PubMed [citation]

Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.

Caminsky NG, Mucaki EJ, Perri AM, Lu R, Knoll JH, Rogan PK.

Hum Mutat. 2016 Jul;37(7):640-52. doi: 10.1002/humu.22972. Epub 2016 Mar 18.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000218725.9

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


This sequence change replaces arginine with cysteine at codon 692 of the ATM protein (p.Arg692Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs765965513, ExAC 0.002%). This variant has been observed in individuals at risk for hereditary breast and/or ovarian cancer as well as in unaffected controls (PMID: 28652578, 26898890). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Oct 30, 2021

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