NM_000051.4(ATM):c.2141C>T (p.Thr714Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 5, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000569489.5

Allele description [Variation Report for NM_000051.4(ATM):c.2141C>T (p.Thr714Ile)]

NM_000051.4(ATM):c.2141C>T (p.Thr714Ile)

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.2141C>T (p.Thr714Ile)

HGVS:

NC_000011.10:g.108256231C>T
NG_009830.1:g.38400C>T
NM_000051.4:c.2141C>TMANE SELECT
NM_001351834.2:c.2141C>T
NP_000042.3:p.Thr714Ile
NP_000042.3:p.Thr714Ile
NP_001338763.1:p.Thr714Ile
LRG_135t1:c.2141C>T
LRG_135:g.38400C>T
LRG_135p1:p.Thr714Ile
NC_000011.9:g.108126958C>T
NM_000051.3:c.2141C>T

Protein change:

T714I

Links:

dbSNP: rs1555074846

NCBI 1000 Genomes Browser:

rs1555074846

Molecular consequence:

NM_000051.4:c.2141C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.2141C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000665594	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Jan 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000904682	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 21, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000665594

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Jan 5, 2022)

germline

clinical testing

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

Citation Link,

SCV000904682

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 21, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

The identification of pathogenic variants in BRCA1/2 negative, high risk, hereditary breast and/or ovarian cancer patients: High frequency of FANCM pathogenic variants.

Schubert S, van Luttikhuizen JL, Auber B, Schmidt G, Hofmann W, Penkert J, Davenport CF, Hille-Betz U, Wendeburg L, Bublitz J, Tauscher M, Hackmann K, Schröck E, Scholz C, Wallaschek H, Schlegelberger B, Illig T, Steinemann D.

Int J Cancer. 2019 Jun 1;144(11):2683-2694. doi: 10.1002/ijc.31992. Epub 2019 Jan 11.

PubMed [citation]

PMID:: 30426508

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000665594.4

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

Description

The p.T714I variant (also known as c.2141C>T), located in coding exon 13 of the ATM gene, results from a C to T substitution at nucleotide position 2141. The threonine at codon 714 is replaced by isoleucine, an amino acid with similar properties. This alteration was detected in a patient with bilateral breast cancer at 35; however, this patient was also found to carry a pathogenic alteration in the PTEN gene (Schubert S et al. Int J Cancer, 2019 06;144:2683-2694). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated 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	1	not provided	not provided		1	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000904682.2

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

#	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: Mar 5, 2024

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