NM_000051.4(ATM):c.7929A>T (p.Lys2643Asn) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 9, 2022
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:: RCV000526758.15

Allele description [Variation Report for NM_000051.4(ATM):c.7929A>T (p.Lys2643Asn)]

NM_000051.4(ATM):c.7929A>T (p.Lys2643Asn)

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.7929A>T (p.Lys2643Asn)

HGVS:

NC_000011.10:g.108333887A>T
NG_009830.1:g.116056A>T
NG_054724.1:g.140946T>A
NM_000051.4:c.7929A>TMANE SELECT
NM_001330368.2:c.641-24816T>A
NM_001351110.2:c.*38+1333T>A
NM_001351834.2:c.7929A>T
NP_000042.3:p.Lys2643Asn
NP_000042.3:p.Lys2643Asn
NP_001338763.1:p.Lys2643Asn
LRG_135t1:c.7929A>T
LRG_135:g.116056A>T
LRG_135p1:p.Lys2643Asn
NC_000011.9:g.108204614A>T
NM_000051.3:c.7929A>T

Protein change:

K2643N

Links:

dbSNP: rs780247224

NCBI 1000 Genomes Browser:

rs780247224

Molecular consequence:

NM_001330368.2:c.641-24816T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+1333T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7929A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7929A>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000622787	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002076011	Natera, Inc.	no assertion criteria provided	Uncertain significance (Oct 28, 2019)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000622787

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 9, 2022)

germline

clinical testing

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

SCV002076011

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Oct 28, 2019)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000622787.4

#	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 lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 2643 of the ATM protein (p.Lys2643Asn). This variant is present in population databases (rs780247224, gnomAD 0.01%). 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: 453710). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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., SCV002076011.1

#	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: Nov 10, 2024

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