NM_000051.4(ATM):c.7397C>T (p.Ala2466Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 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:: RCV002380480.9

Allele description [Variation Report for NM_000051.4(ATM):c.7397C>T (p.Ala2466Val)]

NM_000051.4(ATM):c.7397C>T (p.Ala2466Val)

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.7397C>T (p.Ala2466Val)

HGVS:

NC_000011.10:g.108330303C>T
NG_009830.1:g.112472C>T
NG_054724.1:g.144530G>A
NM_000051.4:c.7397C>TMANE SELECT
NM_001330368.2:c.641-21232G>A
NM_001351110.2:c.*38+4917G>A
NM_001351834.2:c.7397C>T
NP_000042.3:p.Ala2466Val
NP_000042.3:p.Ala2466Val
NP_001338763.1:p.Ala2466Val
LRG_135t1:c.7397C>T
LRG_135:g.112472C>T
LRG_135p1:p.Ala2466Val
NC_000011.9:g.108201030C>T
NM_000051.3:c.7397C>T

Protein change:

A2466V

Molecular consequence:

NM_001330368.2:c.641-21232G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+4917G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7397C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7397C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002673516	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11746755, 17517479 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002673516

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 13, 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

Screening breast cancer patients for ATM mutations and polymorphisms by using denaturing high-performance liquid chromatography.

Atencio DP, Iannuzzi CM, Green S, Stock RG, Bernstein JL, Rosenstein BS.

Environ Mol Mutagen. 2001;38(2-3):200-8.

PubMed [citation]

PMID:: 11746755

Possession of ATM sequence variants as predictor for late normal tissue responses in breast cancer patients treated with radiotherapy.

Ho AY, Fan G, Atencio DP, Green S, Formenti SC, Haffty BG, Iyengar P, Bernstein JL, Stock RG, Cesaretti JA, Rosenstein BS.

Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):677-84. Epub 2007 May 22.

PubMed [citation]

PMID:: 17517479

Details of each submission

From Ambry Genetics, SCV002673516.2

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

Description

The p.A2466V variant (also known as c.7397C>T), located in coding exon 49 of the ATM gene, results from a C to T substitution at nucleotide position 7397. The alanine at codon 2466 is replaced by valine, an amino acid with similar properties. This alteration has been identified in multiple individuals diagnosed with breast cancer (Atencio DP et al. Environ Mol Mutagen, 2001;38:200-8; Ho AY et al. Int J Radiat Oncol Biol Phys, 2007 Nov;69:677-84). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 3, 2024

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