NM_000051.4(ATM):c.3541A>T (p.Lys1181Ter) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Nov 14, 2023
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:: RCV000412416.14

Allele description [Variation Report for NM_000051.4(ATM):c.3541A>T (p.Lys1181Ter)]

NM_000051.4(ATM):c.3541A>T (p.Lys1181Ter)

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.3541A>T (p.Lys1181Ter)

HGVS:

NC_000011.10:g.108281133A>T
NG_009830.1:g.63302A>T
NM_000051.4:c.3541A>TMANE SELECT
NM_001351834.2:c.3541A>T
NP_000042.3:p.Lys1181Ter
NP_000042.3:p.Lys1181Ter
NP_001338763.1:p.Lys1181Ter
LRG_135t1:c.3541A>T
LRG_135:g.63302A>T
LRG_135p1:p.Lys1181Ter
NC_000011.9:g.108151860A>T
NM_000051.3:c.3541A>T

Protein change:

K1181*

Links:

dbSNP: rs1057516981

NCBI 1000 Genomes Browser:

rs1057516981

Molecular consequence:

NM_000051.4:c.3541A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351834.2:c.3541A>T - 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

Recent activity

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MAG TPA_asm: uncultured Actinomycetaceae bacterium isolate DRR247350_bin.14_Meta...
MAG TPA_asm: uncultured Actinomycetaceae bacterium isolate DRR247350_bin.14_MetaWRAP_v1.3_MAG, whole genome shotgun sequencing project
gi|2586416371|tpe|CAUTCJ000000000.1 CJ010000000

Nucleotide
MAG TPA_asm: uncultured Streptococcus sp. isolate DRR247347_bin.24_MetaWRAP_v1.3...
MAG TPA_asm: uncultured Streptococcus sp. isolate DRR247347_bin.24_MetaWRAP_v1.3_MAG, whole genome shotgun sequencing project
gi|2586050497|tpe|CAUTKM000000000.1 KM010000000

Nucleotide
7j65h12.x1 Soares_NSF_F8_9W_OT_PA_P_S1 Homo sapiens cDNA clone IMAGE:3391367 3',...
7j65h12.x1 Soares_NSF_F8_9W_OT_PA_P_S1 Homo sapiens cDNA clone IMAGE:3391367 3', mRNA sequence
gi|10984147|gnl|dbEST|6552567|gb|BF 0.1|

Nucleotide
qa82b11.x1 Soares_fetal_heart_NbHH19W Homo sapiens cDNA clone IMAGE:1693245 3', ...
qa82b11.x1 Soares_fetal_heart_NbHH19W Homo sapiens cDNA clone IMAGE:1693245 3', mRNA sequence
gi|3674711|gnl|dbEST|1905731|gb|AI1 .1|

Nucleotide
Childhood Bladder Cancer Treatment - PDQ Cancer Information Summaries
Childhood Bladder Cancer Treatment - PDQ Cancer Information Summaries

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000486541	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jun 21, 2016)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV000942311	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23807571, 25614872, 18321536, 28492532
SCV003811101	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 24, 2022)	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

SCV000486541

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Jun 21, 2016)

unknown

clinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000942311

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 14, 2023)

germline

clinical testing

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

SCV003811101

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 24, 2022)

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients.

Huang Y, Yang L, Wang J, Yang F, Xiao Y, Xia R, Yuan X, Yan M.

Neuromolecular Med. 2013 Sep;15(3):536-40. doi: 10.1007/s12017-013-8240-3. Epub 2013 Jun 27. Erratum in: Neuromolecular Med. 2014 Mar;16(1):216.

PubMed [citation]

PMID:: 23807571
PMCID:: PMC3732755

Ten new ATM alterations in Polish patients with ataxia-telangiectasia.

Podralska MJ, Stembalska A, Ślęzak R, Lewandowicz-Uszyńska A, Pietrucha B, Kołtan S, Wigowska-Sowińska J, Pilch J, Mosor M, Ziółkowska-Suchanek I, Dzikiewicz-Krawczyk A, Słomski R.

Mol Genet Genomic Med. 2014 Nov;2(6):504-11. doi: 10.1002/mgg3.98. Epub 2014 Jul 30.

PubMed [citation]

PMID:: 25614872
PMCID:: PMC4303220

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000486541.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000942311.6

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

Description

This sequence change creates a premature translational stop signal (p.Lys1181*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 18321536). ClinVar contains an entry for this variant (Variation ID: 371071). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

From Revvity Omics, Revvity, SCV003811101.2

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

#	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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