NM_000051.4(ATM):c.7235A>G (p.Asn2412Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 25, 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:: RCV001358721.10

Allele description [Variation Report for NM_000051.4(ATM):c.7235A>G (p.Asn2412Ser)]

NM_000051.4(ATM):c.7235A>G (p.Asn2412Ser)

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_000051.4(ATM):c.7235A>G (p.Asn2412Ser)

HGVS:

NC_000011.10:g.108329166A>G
NG_009830.1:g.111335A>G
NG_054724.1:g.145667T>C
NM_000051.4:c.7235A>GMANE SELECT
NM_001330368.2:c.641-20095T>C
NM_001351110.2:c.*38+6054T>C
NM_001351834.2:c.7235A>G
NP_000042.3:p.Asn2412Ser
NP_000042.3:p.Asn2412Ser
NP_001338763.1:p.Asn2412Ser
LRG_135t1:c.7235A>G
LRG_135:g.111335A>G
LRG_135p1:p.Asn2412Ser
NC_000011.9:g.108199893A>G
NM_000051.3:c.7235A>G
p.N2412S

Protein change:

N2412S

Links:

dbSNP: rs786203311

NCBI 1000 Genomes Browser:

rs786203311

Molecular consequence:

NM_001330368.2:c.641-20095T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+6054T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7235A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7235A>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
SCV001554559	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28135145, 31159747 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001554559

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 25, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]

PMID:: 31159747
PMCID:: PMC6547505

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001554559.2

#	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.7235A>G (p.Asn2412Ser) results in a 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 4e-06 in 251290 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.7235A>G has been reported in the literature as a VUS in individuals undergoing multigene panel testing for colorectal/breast cancer (example, Yurgelun_2017, Tsaousis_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia or ATM-related cancers. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified 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: Nov 24, 2024

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