NM_000051.4(ATM):c.3806A>G (p.Lys1269Arg) AND Ataxia-telangiectasia syndrome

Clinical significance:Uncertain significance (Last evaluated: Nov 2, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000206887.11

Allele description [Variation Report for NM_000051.4(ATM):c.3806A>G (p.Lys1269Arg)]

NM_000051.4(ATM):c.3806A>G (p.Lys1269Arg)

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.3806A>G (p.Lys1269Arg)
HGVS:
  • NC_000011.10:g.108284286A>G
  • NG_009830.1:g.66455A>G
  • NM_000051.3:c.3806A>G
  • NM_000051.4:c.3806A>GMANE SELECT
  • NM_001351834.2:c.3806A>G
  • NP_000042.3:p.Lys1269Arg
  • NP_000042.3:p.Lys1269Arg
  • NP_001338763.1:p.Lys1269Arg
  • LRG_135t1:c.3806A>G
  • LRG_135:g.66455A>G
  • LRG_135p1:p.Lys1269Arg
  • NC_000011.9:g.108155013A>G
  • p.K1269R
Protein change:
K1269R
Links:
dbSNP: rs146017595
NCBI 1000 Genomes Browser:
rs146017595
Molecular consequence:
  • NM_000051.3:c.3806A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000051.4:c.3806A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.3806A>G - 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
SCV000260024Invitaecriteria provided, single submitter
Uncertain significance
(Nov 2, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000789440Counsylcriteria provided, single submitter
Uncertain significance
(Feb 7, 2017)
unknownclinical testing

Citation Link,

SCV001458193Natera, Inc.no assertion criteria providedUncertain significance
(Sep 16, 2020)
germlineclinical testing

Summary from all submissions

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

Citations

PubMed

Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing.

Dominguez-Valentin M, Nakken S, Tubeuf H, Vodak D, Ekstrøm PO, Nissen AM, Morak M, Holinski-Feder E, Holth A, Capella G, Davidson B, Evans DG, Martins A, Møller P, Hovig E.

Sci Rep. 2019 Dec 6;9(1):18555. doi: 10.1038/s41598-019-54517-z.

PubMed [citation]
PMID:
31811167
PMCID:
PMC6898579

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000260024.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces lysine with arginine at codon 1269 of the ATM protein (p.Lys1269Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs146017595, ExAC 0.02%). This variant has been observed in individual(s) with breast cancer (PMID: 31811167). ClinVar contains an entry for this variant (Variation ID: 185981). 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: Benign; Align-GVGD: Class C2). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 31811167). 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 Counsyl, SCV000789440.1

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

From Natera, Inc., SCV001458193.1

#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: Nov 27, 2021

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