NM_000051.4(ATM):c.3747-3_3751del AND Ataxia-telangiectasia syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 21, 2017
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:: RCV000526399.5

Allele description [Variation Report for NM_000051.4(ATM):c.3747-3_3751del]

NM_000051.4(ATM):c.3747-3_3751del

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.3747-3_3751del

HGVS:

NC_000011.10:g.108284224_108284231del
NC_000011.9:g.108154949_108154956del
NG_009830.1:g.66393_66400del
NM_000051.4:c.3747-3_3751delMANE SELECT
NM_001351834.2:c.3747-3_3751del
LRG_135t1:c.3747-3_3751del
LRG_135:g.66393_66400del
NC_000011.9:g.108154949_108154956del
NC_000011.9:g.108154949_108154956delTTTAGATC
NC_000011.9:g.108154951_108154958del
NM_000051.3:c.3747-3_3751del

Links:

dbSNP: rs1555093256

NCBI 1000 Genomes Browser:

rs1555093256

Molecular consequence:

NM_000051.4:c.3747-3_3751del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001351834.2:c.3747-3_3751del - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV000622451	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 21, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 25614872, 23807571, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000622451

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 21, 2017)

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Ten new ATM alterations in Polish patients with ataxia-telangiectasia.

Podralska MJ, Stembalska A, Ślęzak R, Lewandowicz-Uszyńska A, Pietrucha B, Kołtan S, Wigowska-Sowińska J, Pilch J, Mosor M, Ziółkowska-Suchanek I, Dzikiewicz-Krawczyk A, Słomski R.

Mol Genet Genomic Med. 2014 Nov;2(6):504-11. doi: 10.1002/mgg3.98. Epub 2014 Jul 30.

PubMed [citation]

PMID:: 25614872
PMCID:: PMC4303220

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000622451.4

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

Description

Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals with a ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 26 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted 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

Last Updated: Sep 29, 2024

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