NM_000051.4(ATM):c.2062G>T (p.Glu688Ter) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 18, 2023
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:: RCV001936550.4

Allele description [Variation Report for NM_000051.4(ATM):c.2062G>T (p.Glu688Ter)]

NM_000051.4(ATM):c.2062G>T (p.Glu688Ter)

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.2062G>T (p.Glu688Ter)

HGVS:

NC_000011.10:g.108253977G>T
NG_009830.1:g.36146G>T
NM_000051.4:c.2062G>TMANE SELECT
NM_001351834.2:c.2062G>T
NP_000042.3:p.Glu688Ter
NP_001338763.1:p.Glu688Ter
LRG_135:g.36146G>T
NC_000011.9:g.108124704G>T

Protein change:

E688*

Links:

dbSNP: rs769338089

NCBI 1000 Genomes Browser:

rs769338089

Molecular consequence:

NM_000051.4:c.2062G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.2062G>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002197754	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 18, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 32427313, 23807571, 25614872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002197754

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 18, 2023)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women.

Palmer JR, Polley EC, Hu C, John EM, Haiman C, Hart SN, Gaudet M, Pal T, Anton-Culver H, Trentham-Dietz A, Bernstein L, Ambrosone CB, Bandera EV, Bertrand KA, Bethea TN, Gao C, Gnanaolivu RD, Huang H, Lee KY, LeMarchand L, Na J, Sandler DP, et al.

J Natl Cancer Inst. 2020 Dec 14;112(12):1213-1221. doi: 10.1093/jnci/djaa040. Erratum in: J Natl Cancer Inst. 2020 Oct 1;112(10):1071. doi: 10.1093/jnci/djaa086.

PubMed [citation]

PMID:: 32427313
PMCID:: PMC7735769

Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.

Huang Y, Yang L, Wang J, Yang F, Xiao Y, Xia R, Yuan X, Yan M.

Neuromolecular Med. 2013 Sep;15(3):536-40. doi: 10.1007/s12017-013-8240-3. Epub 2013 Jun 27. Erratum in: Neuromolecular Med. 2014 Mar;16(1):216.

PubMed [citation]

PMID:: 23807571
PMCID:: PMC3732755

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002197754.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1428919). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 32427313). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu688*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).

#	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

Last Updated: Jan 19, 2025

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