NM_000051.4(ATM):c.1898+1G>T AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 11, 2023
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:: RCV000529407.6

Allele description [Variation Report for NM_000051.4(ATM):c.1898+1G>T]

NM_000051.4(ATM):c.1898+1G>T

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.1898+1G>T

HGVS:

NC_000011.10:g.108252913G>T
NG_009830.1:g.35082G>T
NM_000051.4:c.1898+1G>TMANE SELECT
NM_001351834.2:c.1898+1G>T
LRG_135t1:c.1898+1G>T
LRG_135:g.35082G>T
NC_000011.9:g.108123640G>T
NM_000051.3:c.1898+1G>T

Links:

dbSNP: rs758325274

NCBI 1000 Genomes Browser:

rs758325274

Molecular consequence:

NM_000051.4:c.1898+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001351834.2:c.1898+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000622291	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 11, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17985259, 16941484, 29368341, 30549301, 32901917, 28492532
SCV001461016	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000622291

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 11, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001461016

Natera, Inc.

no assertion criteria provided

Pathogenic
(Sep 16, 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

Citations

PubMed

Neuromuscular abnormalities in ataxia telangiectasia: a clinical, electrophysiological and muscle ultrasound study.

Verhagen MM, van Alfen N, Pillen S, Weemaes CM, Yntema JL, Hiel JA, Ter Laak H, van Deuren M, Broeks A, Willemsen MA.

Neuropediatrics. 2007 Jun;38(3):117-21.

PubMed [citation]

PMID:: 17985259

ATM mutations in Italian families with ataxia telangiectasia include two distinct large genomic deletions.

Cavalieri S, Funaro A, Porcedda P, Turinetto V, Migone N, Gatti RA, Brusco A.

Hum Mutat. 2006 Oct;27(10):1061.

PubMed [citation]

PMID:: 16941484

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000622291.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with ataxia-telangiectasia (PMID: 16941484, 17985259). This variant is also known as IVS14 c.1898+1G>T. ClinVar contains an entry for this variant (Variation ID: 453391). Studies have shown that disruption of this splice site results in skipping of skipping of exon 12, but is expected to preserve the integrity of the reading-frame (PMID: 16941484). This variant disrupts a region of the ATM protein in which other variant(s) (p.Leu615Pro) have been determined to be pathogenic (PMID: 29368341, 30549301, 32901917; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This sequence change affects a donor splice site in intron 12 of the ATM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product.

#	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., SCV001461016.1

#	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: Jan 19, 2025

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