NM_000051.4(ATM):c.6841T>C (p.Tyr2281His) AND Ataxia-telangiectasia syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 24, 2021
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:: RCV001210197.13

Allele description

NM_000051.4(ATM):c.6841T>C (p.Tyr2281His)

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.6841T>C (p.Tyr2281His)

HGVS:

NC_000011.10:g.108326091T>C
NG_009830.1:g.108260T>C
NG_054724.1:g.148742A>G
NM_000051.4:c.6841T>CMANE SELECT
NM_001330368.2:c.641-17020A>G
NM_001351110.2:c.*38+9129A>G
NM_001351834.2:c.6841T>C
NP_000042.3:p.Tyr2281His
NP_000042.3:p.Tyr2281His
NP_001338763.1:p.Tyr2281His
LRG_135t1:c.6841T>C
LRG_135:g.108260T>C
LRG_135p1:p.Tyr2281His
NC_000011.9:g.108196818T>C
NM_000051.3:c.6841T>C

Protein change:

Y2281H

Links:

dbSNP: rs1291249685

NCBI 1000 Genomes Browser:

rs1291249685

Molecular consequence:

NM_001330368.2:c.641-17020A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+9129A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.6841T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.6841T>C - 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
SCV001381671	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 24, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002079920	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 25, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001381671

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 24, 2021)

germline

clinical testing

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

SCV002079920

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 25, 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

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 Invitae, SCV001381671.4

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

Description

This sequence change replaces tyrosine with histidine at codon 2281 of the ATM protein (p.Tyr2281His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 490677). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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., SCV002079920.1

#	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: Sep 16, 2024

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