NM_000051.3(ATM):c.8156G>A (p.Arg2719His) AND Ataxia-telangiectasia syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Dec 8, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000232453.6

Allele description

NM_000051.3(ATM):c.8156G>A (p.Arg2719His)

Genes:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.3(ATM):c.8156G>A (p.Arg2719His)

Other names:

p.R2719H:CGT>CAT

HGVS:

NC_000011.10:g.108335849G>A
NG_009830.1:g.118018G>A
NM_000051.3:c.8156G>A
NP_000042.3:p.Arg2719His
LRG_135t1:c.8156G>A
LRG_135:g.118018G>A
LRG_135p1:p.Arg2719His
NC_000011.9:g.108206576G>A
Q13315:p.Arg2719His
p.R2719H

Protein change:

R2719H

Links:

UniProtKB: Q13315#VAR_041581; dbSNP: rs55982963

GMAF:

0.0004(A), 55982963

NCBI 1000 Genomes Browser:

rs55982963

Allele Frequency:

0.00017(A)

Molecular consequence:

NM_000051.3:c.8156G>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:: MedGen: C0004135; Orphanet: 100; OMIM: 208900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000283074	Invitae	criteria provided, single submitter (Nykamp K et al. (Genet Med 2017))	Uncertain significance (Dec 8, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21445571, 19781682, 18384426, 28492532
SCV000734791	Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV000745134	DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Uncertain significance (Jul 27, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000283074

Invitae

criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))

Uncertain significance
(Dec 8, 2017)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV000734791

Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus

no assertion criteria provided

Uncertain significance

germline

clinical testing

SCV000745134

DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus

criteria provided, single submitter

(ACGS Guidelines, 2013)

Uncertain significance
(Jul 27, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline ATM mutational analysis in BRCA1/BRCA2 negative hereditary breast cancer families by MALDI-TOF mass spectrometry.

Graña B, Fachal L, Darder E, Balmaña J, Ramón Y Cajal T, Blanco I, Torres A, Lázaro C, Diez O, Alonso C, Santamariña M, Velasco A, Teulé A, Lasa A, Blanco A, Izquierdo A, Borràs J, Gutiérrez-Enríquez S, Vega A, Brunet J.

Breast Cancer Res Treat. 2011 Jul;128(2):573-9. doi: 10.1007/s10549-011-1462-x. Epub 2011 Mar 29.

PubMed [citation]

PMID:: 21445571

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

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000283074.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine with histidine at codon 2719 of the ATM protein (p.Arg2719His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs55982963, ExAC 0.1%). This variant has been reported in several individuals affected with breast cancer (PMID: 18384426, 19781682, 21445571). ClinVar contains an entry for this variant (Variation ID: 127456). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus, SCV000734791.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus, SCV000745134.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 21, 2018

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