NM_000051.4(ATM):c.5692C>T (p.Arg1898Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 13, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000571941.8

Allele description [Variation Report for NM_000051.4(ATM):c.5692C>T (p.Arg1898Ter)]

NM_000051.4(ATM):c.5692C>T (p.Arg1898Ter)

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.5692C>T (p.Arg1898Ter)

HGVS:

NC_000011.10:g.108307914C>T
NG_009830.1:g.90083C>T
NG_054724.1:g.166919G>A
NM_000051.4:c.5692C>TMANE SELECT
NM_001351834.2:c.5692C>T
NP_000042.3:p.Arg1898Ter
NP_000042.3:p.Arg1898Ter
NP_001338763.1:p.Arg1898Ter
LRG_135t1:c.5692C>T
LRG_135:g.90083C>T
LRG_135p1:p.Arg1898Ter
NC_000011.9:g.108178641C>T
NM_000051.3:c.5692C>T

Protein change:

R1898*

Links:

dbSNP: rs775036118

NCBI 1000 Genomes Browser:

rs775036118

Molecular consequence:

NM_000051.4:c.5692C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.5692C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000667807	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 13, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17124347, 23322442, 25077176, 25374739 Citation Link,
SCV000687636	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000667807

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 13, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000687636

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 15, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

DHPLC screening of ATM gene in Italian patients affected by ataxia-telangiectasia: fourteen novel ATM mutations.

Magliozzi M, Piane M, Torrente I, Sinibaldi L, Rizzo G, Savio C, Lulli P, De Luca A, Dallapiccola B, Chessa L.

Dis Markers. 2006;22(4):257-64.

PubMed [citation]

PMID:: 17124347
PMCID:: PMC3862285

Molecular defects in Moroccan patients with ataxia-telangiectasia.

Jeddane L, Ailal F, Dubois-d'Enghien C, Abidi O, Benhsaien I, Kili A, Chaouki S, Kriouile Y, El Hafidi N, Fadil H, Abilkassem R, Rada N, Bousfiha AA, Barakat A, Stoppa-Lyonnet D, Bellaoui H.

Neuromolecular Med. 2013 Jun;15(2):288-94. doi: 10.1007/s12017-013-8218-1. Epub 2013 Jan 16.

PubMed [citation]

PMID:: 23322442

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000667807.5

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

Description

The p.R1898* pathogenic mutation (also known as c.5692C>T), located in coding exon 37 of the ATM gene, results from a C to T substitution at nucleotide position 5692. This changes the amino acid from an arginine to a stop codon within coding exon 37. This pathogenic mutation has been reported in the literature in conjunction with other ATM mutations in multiple individuals with ataxia telangiectasia (Magliozzi M et al. Dis. Markers 2006; 22(4):257-64; Jeddane L et al. Neuromolecular Med. 2013 Jun;15(2):288-94; Nespoli L et al. Case Reports Immunol 2013;2013:296827.doi:10.1155/2013/296827; Nakamura K et al. Mol Genet Genomic Med 2014 Jul;2(4):332-40). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000687636.3

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

Description

This variant changes 1 nucleotide in exon 38 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 2/251006 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is 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 29, 2024

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