NM_000051.4(ATM):c.2606C>G (p.Ala869Gly) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jan 30, 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:: RCV000476653.18

Allele description [Variation Report for NM_000051.4(ATM):c.2606C>G (p.Ala869Gly)]

NM_000051.4(ATM):c.2606C>G (p.Ala869Gly)

Gene:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.2606C>G (p.Ala869Gly)

Other names:

NP_000042.3:p.Ala869Gly

HGVS:

NC_000011.10:g.108267310C>G
NG_009830.1:g.49479C>G
NM_000051.4:c.2606C>GMANE SELECT
NM_001351834.2:c.2606C>G
NP_000042.3:p.Ala869Gly
NP_000042.3:p.Ala869Gly
NP_001338763.1:p.Ala869Gly
LRG_135t1:c.2606C>G
LRG_135:g.49479C>G
LRG_135p1:p.Ala869Gly
NC_000011.9:g.108138037C>G
NM_000051.3:c.2606C>G
p.A869G

Protein change:

A869G

Links:

dbSNP: rs145513717

NCBI 1000 Genomes Browser:

rs145513717

Molecular consequence:

NM_000051.4:c.2606C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.2606C>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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Human calcium-dependent phospholipid-binding protein (PLA2) mRNA, complete cds
Human calcium-dependent phospholipid-binding protein (PLA2) mRNA, complete cds
gi|190006|gb|M72393.1|HUMPLA2A

Nucleotide
Human endoperoxide synthase type II mRNA, complete cds
Human endoperoxide synthase type II mRNA, complete cds
gi|291987|gb|L15326.1|HUMENDOSYN

Nucleotide
Homo sapiens G protein-coupled receptor 25 (GPR25), mRNA
Homo sapiens G protein-coupled receptor 25 (GPR25), mRNA
gi|1653960909|ref|NM_005298.4|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547002	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 30, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000838508	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV002076320	Natera, Inc.	no assertion criteria provided	Uncertain significance (Mar 6, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547002

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 30, 2024)

germline

clinical testing

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

SCV000838508

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(Jul 2, 2018)

unknown

clinical testing

Citation Link,

SCV002076320

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Mar 6, 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
not provided	unknown	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, SCV000547002.11

#	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 alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 869 of the ATM protein (p.Ala869Gly). This variant is present in population databases (rs145513717, gnomAD 0.05%). 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: 184982). 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 Mendelics, SCV000838508.2

#	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., SCV002076320.1

#	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 8, 2024

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