NM_000051.4(ATM):c.3295G>A (p.Asp1099Asn) AND Ataxia-telangiectasia syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000168114.11

Allele description [Variation Report for NM_000051.4(ATM):c.3295G>A (p.Asp1099Asn)]

NM_000051.4(ATM):c.3295G>A (p.Asp1099Asn)

Gene:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.3295G>A (p.Asp1099Asn)
HGVS:
  • NC_000011.10:g.108279501G>A
  • NG_009830.1:g.61670G>A
  • NM_000051.3:c.3295G>A
  • NM_000051.4:c.3295G>AMANE SELECT
  • NM_001351834.2:c.3295G>A
  • NP_000042.3:p.Asp1099Asn
  • NP_000042.3:p.Asp1099Asn
  • NP_001338763.1:p.Asp1099Asn
  • LRG_135t1:c.3295G>A
  • LRG_135:g.61670G>A
  • LRG_135p1:p.Asp1099Asn
  • NC_000011.9:g.108150228G>A
Protein change:
D1099N
Links:
dbSNP: rs372966951
NCBI 1000 Genomes Browser:
rs372966951
Molecular consequence:
  • NM_000051.3:c.3295G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000051.4:c.3295G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.3295G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Ataxia-telangiectasia syndrome (AT)
Synonyms:
Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:
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)
OriginMethodCitations
SCV000218770Invitaecriteria provided, single submitter
Uncertain significance
(Oct 30, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001457136Natera, Inc.no assertion criteria providedUncertain significance
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

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

Citations

PubMed

Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer.

Tavtigian SV, Oefner PJ, Babikyan D, Hartmann A, Healey S, Le Calvez-Kelm F, Lesueur F, Byrnes GB, Chuang SC, Forey N, Feuchtinger C, Gioia L, Hall J, Hashibe M, Herte B, McKay-Chopin S, Thomas A, Vallée MP, Voegele C, Webb PM, Whiteman DC; Australian Cancer Study.; et al.

Am J Hum Genet. 2009 Oct;85(4):427-46. doi: 10.1016/j.ajhg.2009.08.018. Epub 2009 Sep 24.

PubMed [citation]
PMID:
19781682
PMCID:
PMC2756555

Rare variants in the ATM gene and risk of breast cancer.

Goldgar DE, Healey S, Dowty JG, Da Silva L, Chen X, Spurdle AB, Terry MB, Daly MJ, Buys SM, Southey MC, Andrulis I, John EM; BCFR.; kConFab., Khanna KK, Hopper JL, Oefner PJ, Lakhani S, Chenevix-Trench G.

Breast Cancer Res. 2011 Jul 25;13(4):R73. doi: 10.1186/bcr2919.

PubMed [citation]
PMID:
21787400
PMCID:
PMC3236337
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000218770.11

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces aspartic acid with asparagine at codon 1099 of the ATM protein (p.Asp1099Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs372966951, ExAC 0.03%). This variant has been reported in isolated individuals affected with breast cancer (PMID: 19781682, 21787400, 30093976) and colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 188196). 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 asparagine 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.

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

From Natera, Inc., SCV001457136.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 30, 2021

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