NM_000051.4(ATM):c.5009C>T (p.Ala1670Val) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 8, 2024
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:: RCV001171473.7

Allele description [Variation Report for NM_000051.4(ATM):c.5009C>T (p.Ala1670Val)]

NM_000051.4(ATM):c.5009C>T (p.Ala1670Val)

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.5009C>T (p.Ala1670Val)

Other names:

p.A1670V:GCT>GTT

HGVS:

NC_000011.10:g.108299717C>T
NG_009830.1:g.81886C>T
NM_000051.4:c.5009C>TMANE SELECT
NM_001351834.2:c.5009C>T
NP_000042.3:p.Ala1670Val
NP_000042.3:p.Ala1670Val
NP_001338763.1:p.Ala1670Val
LRG_135t1:c.5009C>T
LRG_135:g.81886C>T
LRG_135p1:p.Ala1670Val
NC_000011.9:g.108170444C>T
NM_000051.3:c.5009C>T

Protein change:

A1670V

Links:

dbSNP: rs375131360

NCBI 1000 Genomes Browser:

rs375131360

Molecular consequence:

NM_000051.4:c.5009C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.5009C>T - 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
SCV001251387	King Laboratory, University of Washington	no assertion criteria provided	Benign (Sep 1, 2019)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV003800794	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 8, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20305132, 31843900 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001251387

King Laboratory, University of Washington

no assertion criteria provided

Benign
(Sep 1, 2019)

germline

research

PubMed (1)
[See all records that cite this PMID]

SCV003800794

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 8, 2024)

germline

clinical testing

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Characterization of splice-altering mutations in inherited predisposition to cancer.

Casadei S, Gulsuner S, Shirts BH, Mandell JB, Kortbawi HM, Norquist BS, Swisher EM, Lee MK, Goldberg Y, O'Connor R, Tan Z, Pritchard CC, King MC, Walsh T.

Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26798-26807. doi: 10.1073/pnas.1915608116. Epub 2019 Dec 16.

PubMed [citation]

PMID:: 31843900
PMCID:: PMC6936554

Details of each submission

From King Laboratory, University of Washington, SCV001251387.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003800794.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: ATM c.5009C>T (p.Ala1670Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251062 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5009C>T has been reported in the literature in at least one individual affected with Breast Cancer (e.g. Bernstein_2010, Casadei_2019). These report(s) 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. The following publications have been ascertained in the context of this evaluation (PMID: 20305132, 31843900). ClinVar contains an entry for this variant (Variation ID: 127397). 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: Sep 29, 2024

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