NM_000051.4(ATM):c.2639-22_2639-20del AND Ataxia-telangiectasia syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 2024
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:: RCV003500540.1

Allele description

NM_000051.4(ATM):c.2639-22_2639-20del

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.2639-22_2639-20del

HGVS:

NC_000011.10:g.108268388_108268390del
NG_009830.1:g.50557_50559del
NM_000051.4:c.2639-22_2639-20delMANE SELECT
NM_001351834.2:c.2639-22_2639-20del
LRG_135:g.50557_50559del
NC_000011.9:g.108139114_108139116del
NC_000011.9:g.108139115_108139117del
NM_000051.3:c.2639-22_2639-20delAAT

Links:

dbSNP: rs1064795554

NCBI 1000 Genomes Browser:

rs1064795554

Molecular consequence:

NM_000051.4:c.2639-22_2639-20del - intron variant - [Sequence Ontology: SO:0001627]
NM_001351834.2:c.2639-22_2639-20del - intron variant - [Sequence Ontology: SO:0001627]

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
SCV004331490	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26896183, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004331490

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2024)

germline

clinical testing

PubMed (2)
[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

Longitudinal analysis of the neurological features of ataxia-telangiectasia.

Jackson TJ, Chow G, Suri M, Byrd P, Taylor MR, Whitehouse WP.

Dev Med Child Neurol. 2016 Jul;58(7):690-7. doi: 10.1111/dmcn.13052. Epub 2016 Feb 19.

PubMed [citation]

PMID:: 26896183

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004331490.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change falls in intron 17 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of ataxia-telangiectasia (PMID: 26896183). ClinVar contains an entry for this variant (Variation ID: 422096). Studies have shown that this variant results in skipping of exon 18 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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: Sep 16, 2024

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