NM_000051.4(ATM):c.5574G>A (p.Trp1858Ter) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 31, 2021
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:: RCV001892183.4

Allele description [Variation Report for NM_000051.4(ATM):c.5574G>A (p.Trp1858Ter)]

NM_000051.4(ATM):c.5574G>A (p.Trp1858Ter)

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.5574G>A (p.Trp1858Ter)

HGVS:

NC_000011.10:g.108304752G>A
NG_009830.1:g.86921G>A
NM_000051.4:c.5574G>AMANE SELECT
NM_001351834.2:c.5574G>A
NP_000042.3:p.Trp1858Ter
NP_001338763.1:p.Trp1858Ter
LRG_135:g.86921G>A
NC_000011.9:g.108175479G>A

Protein change:

W1858*

Links:

dbSNP: rs2135944112

NCBI 1000 Genomes Browser:

rs2135944112

Molecular consequence:

NM_000051.4:c.5574G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.5574G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002154400	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 31, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10864201, 12105990, 23807571, 25614872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002154400

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 31, 2021)

germline

clinical testing

PubMed (5)
[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

ATM protein and p53-serine 15 phosphorylation in ataxia-telangiectasia (AT) patients and at heterozygotes.

Delia D, Mizutani S, Panigone S, Tagliabue E, Fontanella E, Asada M, Yamada T, Taya Y, Prudente S, Saviozzi S, Frati L, Pierotti MA, Chessa L.

Br J Cancer. 2000 Jun;82(12):1938-45.

PubMed [citation]

PMID:: 10864201
PMCID:: PMC2363260

Detection of ATM gene mutation in human glioma cell line M059J by a rapid frameshift/stop codon assay in yeast.

Tsuchida R, Yamada T, Takagi M, Shimada A, Ishioka C, Katsuki Y, Igarashi T, Chessa L, Delia D, Teraoka H, Mizutani S.

Radiat Res. 2002 Aug;158(2):195-201.

PubMed [citation]

PMID:: 12105990

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002154400.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive ATM-related conditions (PMID: 10864201, 12105990). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp1858*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872).

#	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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