NM_000051.4(ATM):c.6415_6416del (p.Glu2139fs) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 4, 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:: RCV000202419.18

Allele description [Variation Report for NM_000051.4(ATM):c.6415_6416del (p.Glu2139fs)]

NM_000051.4(ATM):c.6415_6416del (p.Glu2139fs)

Genes:

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

Variant type:

Microsatellite

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.6415_6416del (p.Glu2139fs)

HGVS:

NC_000011.10:g.108320019GA[1]
NG_009830.1:g.102188GA[1]
NG_054724.1:g.154812CT[1]
NM_000051.4:c.6415_6416delMANE SELECT
NM_001330368.2:c.641-10948_641-10947del
NM_001351110.2:c.*39-10948_*39-10947del
NM_001351834.2:c.6415_6416del
NP_000042.3:p.Glu2139Ilefs
NP_000042.3:p.Glu2139fs
NP_001338763.1:p.Glu2139fs
LRG_135t1:c.6413_6414GA[1]
LRG_135:g.102188GA[1]
LRG_135p1:p.Glu2139Ilefs
NC_000011.9:g.108190745_108190746del
NC_000011.9:g.108190746GA[1]
NM_000051.3:c.6413_6414GA[1]
NM_000051.3:c.6415_6416del
NM_000051.3:c.6415_6416del
NM_000051.3:c.6415_6416delGA

Protein change:

E2139fs

Links:

dbSNP: rs863225466

NCBI 1000 Genomes Browser:

rs863225466

Molecular consequence:

NM_000051.4:c.6415_6416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351834.2:c.6415_6416del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330368.2:c.641-10948_641-10947del - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*39-10948_*39-10947del - intron variant - [Sequence Ontology: SO:0001627]

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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Gene ID:101537434

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000257479	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 4, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23807571, 25614872, 8755918, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000257479

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 4, 2023)

germline

clinical testing

PubMed (4)
[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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000257479.10

#	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.Glu2139Ilefs*6) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 218278). This variant is also known as 6412delAG. This premature translational stop signal has been observed in individual(s) with ataxia telangiectasia (PMID: 8755918). This variant is not present in population databases (gnomAD no frequency).

#	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 3, 2024

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