NM_000051.4(ATM):c.1880T>G (p.Phe627Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 24, 2019
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:: RCV001193666.1

Allele description [Variation Report for NM_000051.4(ATM):c.1880T>G (p.Phe627Cys)]

NM_000051.4(ATM):c.1880T>G (p.Phe627Cys)

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.1880T>G (p.Phe627Cys)

HGVS:

NC_000011.10:g.108252894T>G
NG_009830.1:g.35063T>G
NM_000051.4:c.1880T>GMANE SELECT
NM_001351834.2:c.1880T>G
NP_000042.3:p.Phe627Cys
NP_000042.3:p.Phe627Cys
NP_001338763.1:p.Phe627Cys
LRG_135t1:c.1880T>G
LRG_135:g.35063T>G
LRG_135p1:p.Phe627Cys
NC_000011.9:g.108123621T>G
NM_000051.3:c.1880T>G

Protein change:

F627C

Links:

dbSNP: rs546087885

NCBI 1000 Genomes Browser:

rs546087885

Molecular consequence:

NM_000051.4:c.1880T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.1880T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001362660	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 24, 2019)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19781682, 20305132, 11996792, 12935922, 28652578 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001362660

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 24, 2019)

germline

clinical testing

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

Citation Link

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

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

Radiation exposure, the ATM Gene, and contralateral breast cancer in the women's environmental cancer and radiation epidemiology study.

Bernstein JL, Haile RW, Stovall M, Boice JD Jr, Shore RE, Langholz B, Thomas DC, Bernstein L, Lynch CF, Olsen JH, Malone KE, Mellemkjaer L, Borresen-Dale AL, Rosenstein BS, Teraoka SN, Diep AT, Smith SA, Capanu M, Reiner AS, Liang X, Gatti RA, Concannon P; et al.

J Natl Cancer Inst. 2010 Apr 7;102(7):475-83. doi: 10.1093/jnci/djq055. Epub 2010 Mar 19.

PubMed [citation]

PMID:: 20305132
PMCID:: PMC2902825

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362660.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Variant summary: ATM c.1880T>G (p.Phe627Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250808 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1880T>G has been reported in the literature in individuals affected with Breast Cancer (Bernstein_2010, Sommer_2003, Tavtigian_2009). These reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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

Last Updated: Jan 13, 2025

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