NM_000051.4(ATM):c.3567del (p.Leu1189_Val1190insTer) AND Ataxia-telangiectasia syndrome

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jan 13, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001261520.8

Allele description [Variation Report for NM_000051.4(ATM):c.3567del (p.Leu1189_Val1190insTer)]

NM_000051.4(ATM):c.3567del (p.Leu1189_Val1190insTer)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.3567del (p.Leu1189_Val1190insTer)

HGVS:

NC_000011.10:g.108281159del
NG_009830.1:g.63328del
NM_000051.4:c.3567delMANE SELECT
NM_001351834.2:c.3567del
NP_000042.3:p.Leu1189_Val1190insTer
NP_001338763.1:p.Leu1189_Val1190insTer
LRG_135:g.63328del
NC_000011.9:g.108151885del
NC_000011.9:g.108151886del
NM_000051.3:c.3567delT

Links:

dbSNP: rs1555091431

NCBI 1000 Genomes Browser:

rs1555091431

Molecular consequence:

NM_000051.4:c.3567del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351834.2:c.3567del - frameshift variant - [Sequence Ontology: SO:0001589]

Functional consequence:

Unknown function

Observations:

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
SCV001424176	Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia	criteria provided, single submitter (Perez et al. (J Hum Genet. 2020))	Uncertain significance	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004375986	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 13, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23807571, 25614872, 33084218, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001424176

Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia

criteria provided, single submitter

(Perez et al. (J Hum Genet. 2020))

Uncertain significance

unknown

clinical testing

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

SCV004375986

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 13, 2024)

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
not provided	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Overwhelming genetic heterogeneity and exhausting molecular diagnostic process in chronic and progressive ataxias: facing it up with an algorithm, a gene, a panel at a time.

Perez Maturo J, Zavala L, Vega P, González-Morón D, Medina N, Salinas V, Rosales J, Córdoba M, Arakaki T, Garretto N, Rodríguez-Quiroga S, Kauffman MA.

J Hum Genet. 2020 Oct;65(10):895-902. doi: 10.1038/s10038-020-0785-z. Epub 2020 Jun 3.

PubMed [citation]

PMID:: 32488064

Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.

Huang Y, Yang L, Wang J, Yang F, Xiao Y, Xia R, Yuan X, Yan M.

Neuromolecular Med. 2013 Sep;15(3):536-40. doi: 10.1007/s12017-013-8240-3. Epub 2013 Jun 27. Erratum in: Neuromolecular Med. 2014 Mar;16(1):216.

PubMed [citation]

PMID:: 23807571
PMCID:: PMC3732755

See all PubMed Citations (5)

Details of each submission

From Consultorio y Laboratorio de Neurogenética, Hospital JM Ramos Mejia, SCV001424176.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004375986.2

#	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 creates a premature translational stop signal (p.Val1190*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 33084218). ClinVar contains an entry for this variant (Variation ID: 546687). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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: Jul 13, 2025

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