NM_000051.4(ATM):c.7999A>T (p.Met2667Leu) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 9, 2024
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:: RCV000806156.20

Allele description [Variation Report for NM_000051.4(ATM):c.7999A>T (p.Met2667Leu)]

NM_000051.4(ATM):c.7999A>T (p.Met2667Leu)

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.7999A>T (p.Met2667Leu)

HGVS:

NC_000011.10:g.108333957A>T
NG_009830.1:g.116126A>T
NG_054724.1:g.140876T>A
NM_000051.4:c.7999A>TMANE SELECT
NM_001330368.2:c.641-24886T>A
NM_001351110.2:c.*38+1263T>A
NM_001351834.2:c.7999A>T
NP_000042.3:p.Met2667Leu
NP_000042.3:p.Met2667Leu
NP_001338763.1:p.Met2667Leu
LRG_135t1:c.7999A>T
LRG_135:g.116126A>T
LRG_135p1:p.Met2667Leu
NC_000011.9:g.108204684A>T
NM_000051.3:c.7999A>T

Protein change:

M2667L

Links:

dbSNP: rs34099398

NCBI 1000 Genomes Browser:

rs34099398

Molecular consequence:

NM_001330368.2:c.641-24886T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+1263T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7999A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7999A>T - 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

Clear Turn Off Turn On

SLC35G2 [Papio anubis]
SLC35G2 [Papio anubis]
Gene ID:101017912

Gene
UDP-Glycosyltransferase superfamily protein [Arabidopsis thaliana]
UDP-Glycosyltransferase superfamily protein [Arabidopsis thaliana]
Gene ID:816790

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000946139	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 9, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30303537, 28492532
SCV002076818	Natera, Inc.	no assertion criteria provided	Uncertain significance (Aug 26, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000946139

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 9, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002076818

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Aug 26, 2020)

germline

clinical testing

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

Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.

Girard E, Eon-Marchais S, Olaso R, Renault AL, Damiola F, Dondon MG, Barjhoux L, Goidin D, Meyer V, Le Gal D, Beauvallet J, Mebirouk N, Lonjou C, Coignard J, Marcou M, Cavaciuti E, Baulard C, Bihoreau MT, Cohen-Haguenauer O, Leroux D, Penet C, Fert-Ferrer S, et al.

Int J Cancer. 2019 Apr 15;144(8):1962-1974. doi: 10.1002/ijc.31921. Epub 2018 Nov 13.

PubMed [citation]

PMID:: 30303537
PMCID:: PMC6587727

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000946139.6

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2667 of the ATM protein (p.Met2667Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30303537). ClinVar contains an entry for this variant (Variation ID: 479035). 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 tolerated. 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 Natera, Inc., SCV002076818.1

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine