NM_000051.4(ATM):c.68G>A (p.Arg23Gln) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 18, 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:: RCV000230719.11

Allele description [Variation Report for NM_000051.4(ATM):c.68G>A (p.Arg23Gln)]

NM_000051.4(ATM):c.68G>A (p.Arg23Gln)

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.68G>A (p.Arg23Gln)

Other names:

p.R23Q:CGA>CAA

HGVS:

NC_000011.10:g.108227692G>A
NG_009830.1:g.9861G>A
NM_000051.4:c.68G>AMANE SELECT
NM_001351834.2:c.68G>A
NM_001351835.2:c.68G>A
NM_001351836.2:c.68G>A
NP_000042.3:p.Arg23Gln
NP_000042.3:p.Arg23Gln
NP_001338763.1:p.Arg23Gln
NP_001338764.1:p.Arg23Gln
NP_001338765.1:p.Arg23Gln
LRG_135t1:c.68G>A
LRG_135:g.9861G>A
LRG_135p1:p.Arg23Gln
NC_000011.9:g.108098419G>A
NM_000051.3:c.68G>A
Q13315:p.Arg23Gln
p.R23Q

Protein change:

R23Q

Links:

UniProtKB: Q13315#VAR_041545; dbSNP: rs587779858

NCBI 1000 Genomes Browser:

rs587779858

Molecular consequence:

NM_000051.4:c.68G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.68G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351835.2:c.68G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351836.2:c.68G>A - 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
SCV000283028	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 18, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30303537, 31050087, 32068069, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000283028

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 18, 2022)

germline

clinical testing

PubMed (4)
[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

Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.

Girard E, Eon-Marchais S, Olaso R, Renault AL, Damiola F, Dondon MG, Barjhoux L, Goidin D, Meyer V, Le Gal D, Beauvallet J, Mebirouk N, Lonjou C, Coignard J, Marcou M, Cavaciuti E, Baulard C, Bihoreau MT, Cohen-Haguenauer O, Leroux D, Penet C, Fert-Ferrer S, et al.

Int J Cancer. 2019 Apr 15;144(8):1962-1974. doi: 10.1002/ijc.31921. Epub 2018 Nov 13.

PubMed [citation]

PMID:: 30303537
PMCID:: PMC6587727

Functional classification of ATM variants in ataxia-telangiectasia patients.

Fiévet A, Bellanger D, Rieunier G, Dubois d'Enghien C, Sophie J, Calvas P, Carriere JP, Anheim M, Castrioto A, Flabeau O, Degos B, Ewenczyk C, Mahlaoui N, Touzot F, Suarez F, Hully M, Roubertie A, Aladjidi N, Tison F, Antoine-Poirel H, Dahan K, Doummar D, et al.

Hum Mutat. 2019 Oct;40(10):1713-1730. doi: 10.1002/humu.23778. Epub 2019 May 17.

PubMed [citation]

PMID:: 31050087

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000283028.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 23 of the ATM protein (p.Arg23Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with a personal/family history of breast/ovarian cancer and clinical features of ataxia-telangiectasia (PMID: 30303537, 31050087, 32068069). ClinVar contains an entry for this variant (Variation ID: 127429). 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 disruptive. 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: Feb 20, 2024

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