NM_000051.4(ATM):c.2638+1G>T AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 28, 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:: RCV001376915.8

Allele description [Variation Report for NM_000051.4(ATM):c.2638+1G>T]

NM_000051.4(ATM):c.2638+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.2638+1G>T

HGVS:

NC_000011.10:g.108267343G>T
NG_009830.1:g.49512G>T
NM_000051.4:c.2638+1G>TMANE SELECT
NM_001351834.2:c.2638+1G>T
LRG_135:g.49512G>T
NC_000011.9:g.108138070G>T
NM_000051.3:c.2638+1G>T

Links:

dbSNP: rs2135509713

NCBI 1000 Genomes Browser:

rs2135509713

Molecular consequence:

NM_000051.4:c.2638+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001351834.2:c.2638+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
SCV001574110	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31843900, 25122203, 28492532
SCV002078771	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Sep 13, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001574110

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002078771

Natera, Inc.

no assertion criteria provided

Likely pathogenic
(Sep 13, 2021)

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

Characterization of splice-altering mutations in inherited predisposition to cancer.

Casadei S, Gulsuner S, Shirts BH, Mandell JB, Kortbawi HM, Norquist BS, Swisher EM, Lee MK, Goldberg Y, O'Connor R, Tan Z, Pritchard CC, King MC, Walsh T.

Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26798-26807. doi: 10.1073/pnas.1915608116. Epub 2019 Dec 16.

PubMed [citation]

PMID:: 31843900
PMCID:: PMC6936554

The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia.

Méneret A, Ahmar-Beaugendre Y, Rieunier G, Mahlaoui N, Gaymard B, Apartis E, Tranchant C, Rivaud-Péchoux S, Degos B, Benyahia B, Suarez F, Maisonobe T, Koenig M, Durr A, Stern MH, Dubois d'Enghien C, Fischer A, Vidailhet M, Stoppa-Lyonnet D, Grabli D, Anheim M.

Neurology. 2014 Sep 16;83(12):1087-95. doi: 10.1212/WNL.0000000000000794. Epub 2014 Aug 13.

PubMed [citation]

PMID:: 25122203

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001574110.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Studies have shown that disruption of this splice site results in skipping of exon 17 and introduces a premature termination codon (PMID: 31843900). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 1066028). Disruption of this splice site has been observed in individual(s) with ataxia-telangiectasia (A-T) (PMID: 25122203). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 17 of the ATM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. 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

From Natera, Inc., SCV002078771.1

#	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: Sep 29, 2024

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