NM_000051.4(ATM):c.6537T>G (p.Ile2179Met) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Feb 1, 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:: RCV000205267.22

Allele description [Variation Report for NM_000051.4(ATM):c.6537T>G (p.Ile2179Met)]

NM_000051.4(ATM):c.6537T>G (p.Ile2179Met)

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.6537T>G (p.Ile2179Met)

Other names:

NP_000042.3:p.Ile2179Met

HGVS:

NC_000011.10:g.108321385T>G
NG_009830.1:g.103554T>G
NG_054724.1:g.153448A>C
NM_000051.4:c.6537T>GMANE SELECT
NM_001330368.2:c.641-12314A>C
NM_001351110.2:c.*39-12314A>C
NM_001351834.2:c.6537T>G
NP_000042.3:p.Ile2179Met
NP_000042.3:p.Ile2179Met
NP_001338763.1:p.Ile2179Met
LRG_135t1:c.6537T>G
LRG_135:g.103554T>G
LRG_135p1:p.Ile2179Met
NC_000011.9:g.108192112T>G
NM_000051.3:c.6537T>G
p.I2179M

Protein change:

I2179M

Links:

dbSNP: rs146243469

NCBI 1000 Genomes Browser:

rs146243469

Molecular consequence:

NM_001330368.2:c.641-12314A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-12314A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6537T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6537T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ataxia-telangiectasia syndrome (AT)
Synonyms:: Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

Recent activity

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Alba DNA/RNA-binding protein [Arabidopsis thaliana]
Alba DNA/RNA-binding protein [Arabidopsis thaliana]
gi|18397011|ref|NP_564325.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000260111	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 1, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25186627, 35264596, 28492532
SCV000838575	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV001458448	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 16, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000260111

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 1, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000838575

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(Jul 2, 2018)

unknown

clinical testing

Citation Link,

SCV001458448

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 16, 2020)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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

Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.

Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR.

Cancer. 2015 Jan 1;121(1):25-33. doi: 10.1002/cncr.29010. Epub 2014 Sep 3.

PubMed [citation]

PMID:: 25186627

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Guindalini RSC, Viana DV, Kitajima JPFW, Rocha VM, López RVM, Zheng Y, Freitas É, Monteiro FPM, Valim A, Schlesinger D, Kok F, Olopade OI, Folgueira MAAK.

Sci Rep. 2022 Mar 9;12(1):4190. doi: 10.1038/s41598-022-07383-1.

PubMed [citation]

PMID:: 35264596
PMCID:: PMC8907244

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000260111.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2179 of the ATM protein (p.Ile2179Met). This variant is present in population databases (rs146243469, gnomAD 0.05%). This missense change has been observed in individual(s) with breast cancer (PMID: 25186627, 35264596). ClinVar contains an entry for this variant (Variation ID: 186221). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant 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 Mendelics, SCV000838575.2

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

#	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

From Natera, Inc., SCV001458448.1

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

#	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: Jul 15, 2024

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