NM_000051.4(ATM):c.4095_4096del (p.Leu1365_Cys1366insTer) AND Ataxia-telangiectasia syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 29, 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:: RCV000666871.3

Allele description [Variation Report for NM_000051.4(ATM):c.4095_4096del (p.Leu1365_Cys1366insTer)]

NM_000051.4(ATM):c.4095_4096del (p.Leu1365_Cys1366insTer)

Gene:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.4095_4096del (p.Leu1365_Cys1366insTer)

HGVS:

NC_000011.10:g.108287699CT[1]
NG_009830.1:g.69868CT[1]
NM_000051.4:c.4095_4096delMANE SELECT
NM_001351834.2:c.4095_4096del
NP_000042.3:p.Leu1365_Cys1366insTer
NP_001338763.1:p.Leu1365_Cys1366insTer
LRG_135:g.69868CT[1]
NC_000011.9:g.108158426CT[1]
NC_000011.9:g.108158426_108158427del
NM_000051.3:c.4095_4096delCT

Links:

dbSNP: rs1555096057

NCBI 1000 Genomes Browser:

rs1555096057

Molecular consequence:

NM_000051.4:c.4095_4096del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001351834.2:c.4095_4096del - frameshift variant - [Sequence Ontology: SO:0001589]

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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MGAT3 [Ursus arctos]
MGAT3 [Ursus arctos]
Gene ID:113241760

Gene
PGM5 [Ursus arctos]
PGM5 [Ursus arctos]
Gene ID:113270190

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000791235	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (May 5, 2017)	unknown	clinical testing	Citation Link,
SCV004489699	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 29, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 32255556, 23807571, 25614872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000791235

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(May 5, 2017)

unknown

clinical testing

Citation Link,

SCV004489699

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 29, 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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Burden of hereditary cancer susceptibility in unselected patients with pancreatic ductal adenocarcinoma referred for germline screening.

Cremin C, Lee MK, Hong Q, Hoeschen C, Mackenzie A, Dixon K, McCullum M, Nuk J, Kalloger S, Karasinska J, Scudamore C, Kim PTW, Donnellan F, Lam ECS, Lim HJ, Neben CL, Stedden W, Zhou AY, Schaeffer DF, Sun S, Renouf DJ, Schrader KA.

Cancer Med. 2020 Jun;9(11):4004-4013. doi: 10.1002/cam4.2973. Epub 2020 Apr 7.

PubMed [citation]

PMID:: 32255556
PMCID:: PMC7286471

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

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000791235.1

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

#	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, SCV004489699.1

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

Description

This variant is also known as c.4098_4099delTG. ClinVar contains an entry for this variant (Variation ID: 551735). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with familial pancreatic cancer (PMID: 32255556). This sequence change creates a premature translational stop signal (p.Cys1366*) 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).

#	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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