NM_000051.4(ATM):c.1009C>T (p.Arg337Cys) AND Familial cancer of breast

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 27, 2024
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:: RCV001762215.8

Allele description [Variation Report for NM_000051.4(ATM):c.1009C>T (p.Arg337Cys)]

NM_000051.4(ATM):c.1009C>T (p.Arg337Cys)

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.1009C>T (p.Arg337Cys)

Other names:

p.R337C:CGT>TGT

HGVS:

NC_000011.10:g.108247071C>T
NG_009830.1:g.29240C>T
NM_000051.4:c.1009C>TMANE SELECT
NM_001351834.2:c.1009C>T
NP_000042.3:p.Arg337Cys
NP_000042.3:p.Arg337Cys
NP_001338763.1:p.Arg337Cys
LRG_135t1:c.1009C>T
LRG_135:g.29240C>T
LRG_135p1:p.Arg337Cys
NC_000011.9:g.108117798C>T
NM_000051.3:c.1009C>T
Q13315:p.Arg337Cys
p.R337C

Protein change:

R337C

Links:

UniProtKB: Q13315#VAR_041549; dbSNP: rs138398778

NCBI 1000 Genomes Browser:

rs138398778

Molecular consequence:

NM_000051.4:c.1009C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.1009C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002580517	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004171463	St. Jude Molecular Pathology, St. Jude Children's Research Hospital	criteria provided, single submitter (St. Jude Assertion Criteria 2020)	Uncertain significance (Oct 16, 2023)	germline	clinical testing	Citation Link,
SCV004206466	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 27, 2024)	unknown	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

SCV002580517

MGZ Medical Genetics Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 28, 2021)

germline

clinical testing

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

SCV004171463

St. Jude Molecular Pathology, St. Jude Children's Research Hospital

criteria provided, single submitter

(St. Jude Assertion Criteria 2020)

Uncertain significance
(Oct 16, 2023)

germline

clinical testing

Citation Link,

SCV004206466

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 27, 2024)

unknown

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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 MGZ Medical Genetics Center, SCV002580517.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV004171463.1

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

Description

The ATM c.1009C>T (p.Arg337Cys) missense change has a maximum subpopulation frequency of 0.019% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. This variant has been reported in individuals with breast cancer (PMID: 19781682, 30303537). To our knowledge, this variant has not been reported in individuals with ataxia telangiectasia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of 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

From Baylor Genetics, SCV004206466.2

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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