NM_000051.4(ATM):c.6056A>G (p.Tyr2019Cys) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 16, 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:: RCV000543617.16

Allele description [Variation Report for NM_000051.4(ATM):c.6056A>G (p.Tyr2019Cys)]

NM_000051.4(ATM):c.6056A>G (p.Tyr2019Cys)

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.6056A>G (p.Tyr2019Cys)

HGVS:

NC_000011.10:g.108315872A>G
NG_009830.1:g.98041A>G
NG_054724.1:g.158961T>C
NM_000051.4:c.6056A>GMANE SELECT
NM_001330368.2:c.641-6801T>C
NM_001351110.2:c.*39-6801T>C
NM_001351834.2:c.6056A>G
NP_000042.3:p.Tyr2019Cys
NP_000042.3:p.Tyr2019Cys
NP_001338763.1:p.Tyr2019Cys
LRG_135t1:c.6056A>G
LRG_135:g.98041A>G
LRG_135p1:p.Tyr2019Cys
NC_000011.9:g.108186599A>G
NM_000051.3:c.6056A>G

Protein change:

Y2019C

Links:

dbSNP: rs876658415

NCBI 1000 Genomes Browser:

rs876658415

Molecular consequence:

NM_001330368.2:c.641-6801T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-6801T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6056A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6056A>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000622634	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 16, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22649200, 26896183, 30549301, 19431188, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000622634

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 16, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95.

Carney EF, Srinivasan V, Moss PA, Taylor AM.

J Immunol. 2012 Jul 1;189(1):261-8. doi: 10.4049/jimmunol.1101909. Epub 2012 May 30.

PubMed [citation]

PMID:: 22649200

Longitudinal analysis of the neurological features of ataxia-telangiectasia.

Jackson TJ, Chow G, Suri M, Byrd P, Taylor MR, Whitehouse WP.

Dev Med Child Neurol. 2016 Jul;58(7):690-7. doi: 10.1111/dmcn.13052. Epub 2016 Feb 19.

PubMed [citation]

PMID:: 26896183

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000622634.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2019 of the ATM protein (p.Tyr2019Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ataxia-telangiectasia (PMID: 19431188, 22649200, 26896183, 30549301). ClinVar contains an entry for this variant (Variation ID: 230152). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATM protein function. Experimental studies have shown that this missense change affects ATM function (PMID: 19431188). 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

Last Updated: Jul 5, 2025

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