NM_000051.4(ATM):c.2087G>T (p.Gly696Val) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 2020
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:: RCV001359376.7

Allele description [Variation Report for NM_000051.4(ATM):c.2087G>T (p.Gly696Val)]

NM_000051.4(ATM):c.2087G>T (p.Gly696Val)

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.2087G>T (p.Gly696Val)

HGVS:

NC_000011.10:g.108254002G>T
NG_009830.1:g.36171G>T
NM_000051.4:c.2087G>TMANE SELECT
NM_001351834.2:c.2087G>T
NP_000042.3:p.Gly696Val
NP_001338763.1:p.Gly696Val
LRG_135:g.36171G>T
NC_000011.9:g.108124729G>T

Protein change:

G696V

Links:

dbSNP: rs752550257

NCBI 1000 Genomes Browser:

rs752550257

Molecular consequence:

NM_000051.4:c.2087G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.2087G>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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nssv3567713 (0)
MeSH
Day_0_Control_3_R1_E3
Day_0_Control_3_R1_E3

biosample
PREDICTED: Rattus norvegicus ATP binding cassette subfamily C member 3 (Abcc3), ...
PREDICTED: Rattus norvegicus ATP binding cassette subfamily C member 3 (Abcc3), transcript variant X10, misc_RNA
gi|2678876531|ref|XR_005489680.2|

Nucleotide
ATP-binding cassette sub-family C member 3 isoform X2 [Rattus norvegicus]
ATP-binding cassette sub-family C member 3 isoform X2 [Rattus norvegicus]
gi|1046848297|ref|XP_017452457.1|

Protein
PREDICTED: Cucumis sativus NDR1/HIN1-like protein 1 (LOC101212136), mRNA
PREDICTED: Cucumis sativus NDR1/HIN1-like protein 1 (LOC101212136), mRNA
gi|1784850562|ref|XM_004139544.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001555241	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 13, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001555241

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 13, 2020)

germline

clinical testing

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

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, SCV001555241.4

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

Description

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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces glycine with valine at codon 696 of the ATM protein (p.Gly696Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Sep 29, 2024

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