NM_000051.4(ATM):c.6820G>A (p.Ala2274Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Sep 6, 2018
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:: RCV000159644.18

Allele description [Variation Report for NM_000051.4(ATM):c.6820G>A (p.Ala2274Thr)]

NM_000051.4(ATM):c.6820G>A (p.Ala2274Thr)

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.6820G>A (p.Ala2274Thr)

Other names:

p.A2274T:GCA>ACA

HGVS:

NC_000011.10:g.108326070G>A
NG_009830.1:g.108239G>A
NG_054724.1:g.148763C>T
NM_000051.4:c.6820G>AMANE SELECT
NM_001330368.2:c.641-16999C>T
NM_001351110.2:c.*38+9150C>T
NM_001351834.2:c.6820G>A
NP_000042.3:p.Ala2274Thr
NP_000042.3:p.Ala2274Thr
NP_001338763.1:p.Ala2274Thr
LRG_135t1:c.6820G>A
LRG_135:g.108239G>A
LRG_135p1:p.Ala2274Thr
NC_000011.9:g.108196797G>A
NM_000051.3:c.6820G>A
Q13315:p.Ala2274Thr
p.A2274T

Protein change:

A2274T

Links:

UniProtKB: Q13315#VAR_010848; dbSNP: rs567060474

NCBI 1000 Genomes Browser:

rs567060474

Molecular consequence:

NM_001330368.2:c.641-16999C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+9150C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6820G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6820G>A - 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
SCV000215124	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Sep 6, 2018)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 11606401, 11805335, 17393301, 18573109, 19431188, 19781682, 21787400, 22529920, 23585524, 27449771 Citation Link,
SCV000910700	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 20, 2016)	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

SCV000215124

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Sep 6, 2018)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link,

SCV000910700

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 20, 2016)

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

Citations

PubMed

Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients.

Dörk T, Bendix R, Bremer M, Rades D, Klöpper K, Nicke M, Skawran B, Hector A, Yamini P, Steinmann D, Weise S, Stuhrmann M, Karstens JH.

Cancer Res. 2001 Oct 15;61(20):7608-15.

PubMed [citation]

PMID:: 11606401

Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer.

Scott SP, Bendix R, Chen P, Clark R, Dork T, Lavin MF.

Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):925-30.

PubMed [citation]

PMID:: 11805335
PMCID:: PMC117407

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000215124.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000910700.1

#	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: Nov 3, 2024

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