NM_000051.4(ATM):c.2650C>T (p.Pro884Ser) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 13, 2022
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:: RCV003107840.4

Allele description [Variation Report for NM_000051.4(ATM):c.2650C>T (p.Pro884Ser)]

NM_000051.4(ATM):c.2650C>T (p.Pro884Ser)

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.2650C>T (p.Pro884Ser)

HGVS:

NC_000011.10:g.108268421C>T
NG_009830.1:g.50590C>T
NM_000051.4:c.2650C>TMANE SELECT
NM_001351834.2:c.2650C>T
NP_000042.3:p.Pro884Ser
NP_001338763.1:p.Pro884Ser
LRG_135t1:c.2650C>T
LRG_135:g.50590C>T
NC_000011.9:g.108139148C>T
NM_000051.3:c.2650C>T

Protein change:

P884S

Links:

dbSNP: rs1591593623

NCBI 1000 Genomes Browser:

rs1591593623

Molecular consequence:

NM_000051.4:c.2650C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.2650C>T - 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

Recent activity

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Rattus norvegicus neurofibromin 1 (Nf1), mRNA
Rattus norvegicus neurofibromin 1 (Nf1), mRNA
gi|6981263|ref|NM_012609.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003783656	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17393301, 19781682, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003783656

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 13, 2022)

germline

clinical testing

PubMed (3)
[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

The spectrum of ATM missense variants and their contribution to contralateral breast cancer.

Broeks A, Braaf LM, Huseinovic A, Schmidt MK, Russell NS, van Leeuwen FE, Hogervorst FB, Van 't Veer LJ.

Breast Cancer Res Treat. 2008 Jan;107(2):243-8. Epub 2007 Mar 28.

PubMed [citation]

PMID:: 17393301
PMCID:: PMC2137941

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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003783656.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 1303049). This missense change has been observed in individual(s) with breast cancer (PMID: 17393301, 19781682). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 884 of the ATM protein (p.Pro884Ser).

#	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: Sep 29, 2024

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