NM_000051.4(ATM):c.7915A>T (p.Lys2639Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 13, 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:: RCV004044128.1

Allele description [Variation Report for NM_000051.4(ATM):c.7915A>T (p.Lys2639Ter)]

NM_000051.4(ATM):c.7915A>T (p.Lys2639Ter)

Genes:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.7915A>T (p.Lys2639Ter)

HGVS:

NC_000011.10:g.108332888A>T
NG_009830.1:g.115057A>T
NG_054724.1:g.141945T>A
NM_000051.4:c.7915A>TMANE SELECT
NM_001330368.2:c.641-23817T>A
NM_001351110.2:c.*38+2332T>A
NM_001351834.2:c.7915A>T
NP_000042.3:p.Lys2639Ter
NP_000042.3:p.Lys2639Ter
NP_001338763.1:p.Lys2639Ter
LRG_135t1:c.7915A>T
LRG_135:g.115057A>T
LRG_135p1:p.Lys2639Ter
NC_000011.9:g.108203615A>T
NM_000051.3:c.7915A>T

Protein change:

K2639*

Links:

dbSNP: rs2136572656

NCBI 1000 Genomes Browser:

rs2136572656

Molecular consequence:

NM_001330368.2:c.641-23817T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2332T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7915A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.7915A>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
SCV005020286	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30338439, 37438524 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005020286

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 13, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

The Cerebellar Cognitive Affective Syndrome in Ataxia-Telangiectasia.

Hoche F, Daly MP, Chutake YK, Valera E, Sherman JC, Schmahmann JD.

Cerebellum. 2019 Apr;18(2):225-244. doi: 10.1007/s12311-018-0983-9.

PubMed [citation]

PMID:: 30338439

A framework for individualized splice-switching oligonucleotide therapy.

Kim J, Woo S, de Gusmao CM, Zhao B, Chin DH, DiDonato RL, Nguyen MA, Nakayama T, Hu CA, Soucy A, Kuniholm A, Thornton JK, Riccardi O, Friedman DA, El Achkar CM, Dash Z, Cornelissen L, Donado C, Faour KNW, Bush LW, Suslovitch V, Lentucci C, et al.

Nature. 2023 Jul;619(7971):828-836. doi: 10.1038/s41586-023-06277-0. Epub 2023 Jul 12.

PubMed [citation]

PMID:: 37438524
PMCID:: PMC10371869

Details of each submission

From Ambry Genetics, SCV005020286.1

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

Description

The p.K2639* pathogenic mutation (also known as c.7915A>T), located in coding exon 52 of the ATM gene, results from an A to T substitution at nucleotide position 7915. This changes the amino acid from a lysine to a stop codon within coding exon 52. This variant has been detected in conjunction with an ATM pathogenic variant in at least one individual diagnosed with clinical features of ataxia-telangiectasia; however, the phase of the two variants is unknown (Kim J et al. Nature, 2023 Jul;619:828-836; Hoche F et al. Cerebellum, 2019 Apr;18:225-244). 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

Last Updated: Nov 10, 2024

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