NM_000051.4(ATM):c.8010+1del AND Ataxia-telangiectasia syndrome

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Sep 27, 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:: RCV000475897.24

Allele description [Variation Report for NM_000051.4(ATM):c.8010+1del]

NM_000051.4(ATM):c.8010+1del

Genes:

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

Variant type:

Deletion

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.8010+1del

HGVS:

NC_000011.10:g.108333969del
NC_000011.9:g.108204695del
NG_009830.1:g.116138del
NG_054724.1:g.140865del
NM_000051.4:c.8010+1delMANE SELECT
NM_001330368.2:c.641-24897del
NM_001351110.2:c.*38+1252del
NM_001351834.2:c.8010+1del
LRG_135t1:c.8010+1del
LRG_135:g.116138del
NC_000011.9:g.108204695del
NC_000011.9:g.108204695delG
NC_000011.9:g.108204696del
NC_000011.9:g.108204696del
NM_000051.3:c.8010+1del
NM_000051.3:c.8010+1delG

Links:

dbSNP: rs876659350

NCBI 1000 Genomes Browser:

rs876659350

Molecular consequence:

NM_001330368.2:c.641-24897del - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+1252del - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.8010+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001351834.2:c.8010+1del - splice donor variant - [Sequence Ontology: SO:0001575]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000546750	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 27, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 23807571, 25614872, 33919281, 28492532
SCV001138574	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002076840	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Dec 31, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000546750

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 27, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001138574

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV002076840

Natera, Inc.

no assertion criteria provided

Likely pathogenic
(Dec 31, 2020)

germline

clinical testing

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000546750.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a splice site in intron 54 of the ATM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 231769). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 33919281).

#	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 Mendelics, SCV001138574.1

#	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 Natera, Inc., SCV002076840.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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