NM_000051.4(ATM):c.4110-1G>A AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 25, 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:: RCV000462992.14

Allele description [Variation Report for NM_000051.4(ATM):c.4110-1G>A]

NM_000051.4(ATM):c.4110-1G>A

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.4110-1G>A

HGVS:

NC_000011.10:g.108288976G>A
NG_009830.1:g.71145G>A
NM_000051.4:c.4110-1G>AMANE SELECT
NM_001351834.2:c.4110-1G>A
LRG_135t1:c.4110-1G>A
LRG_135:g.71145G>A
NC_000011.9:g.108159703G>A
NM_000051.3:c.4110-1G>A

Links:

dbSNP: rs1060501692

NCBI 1000 Genomes Browser:

rs1060501692

Molecular consequence:

NM_000051.4:c.4110-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001351834.2:c.4110-1G>A - 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

Recent activity

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valosin containing protein (p97)/p47 complex interacting protein 1, partial [Odontophrynus occidentalis]
gi|1304835132|gb|AUD52841.1|

Protein
cytochrome c oxidase subunit I, partial (mitochondrion) [Odontophrynus americanu...
cytochrome c oxidase subunit I, partial (mitochondrion) [Odontophrynus americanus]
gi|400180116|gb|AFP73187.1|

Protein
GPL34583[RGSE] (1)
GEO DataSets
Brain mRNA expression profiling of Atlantic salmon (Salmo salar) age-at-maturity...
Brain mRNA expression profiling of Atlantic salmon (Salmo salar) age-at-maturity-associated genes during different maturation stages
Accession: GSE269678

GEO DataSets
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GBS mastitis in Portugal

biosample

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547109	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 25, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 14695534, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547109

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 25, 2023)

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

Nonclassical splicing mutations in the coding and noncoding regions of the ATM Gene: maximum entropy estimates of splice junction strengths.

Eng L, Coutinho G, Nahas S, Yeo G, Tanouye R, Babaei M, Dörk T, Burge C, Gatti RA.

Hum Mutat. 2004 Jan;23(1):67-76.

PubMed [citation]

PMID:: 14695534

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000547109.9

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

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in altered splicing and introduces a premature termination codon (PMID: 14695534). The resulting mRNA is expected to undergo nonsense-mediated decay. Studies have shown that disruption of this splice site alters ATM gene expression (PMID: 14695534). ClinVar contains an entry for this variant (Variation ID: 407707). This variant is also known as IVS29-1G>A. Disruption of this splice site has been observed in individual(s) with ataxia-telangiectasia (PMID: 14695534). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 27 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.

#	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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