NM_000051.4(ATM):c.7928-2A>G AND Ataxia-telangiectasia syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 22, 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:: RCV001860068.12

Allele description [Variation Report for NM_000051.4(ATM):c.7928-2A>G]

NM_000051.4(ATM):c.7928-2A>G

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.7928-2A>G

HGVS:

NC_000011.10:g.108333884A>G
NG_009830.1:g.116053A>G
NG_054724.1:g.140949T>C
NM_000051.4:c.7928-2A>GMANE SELECT
NM_001330368.2:c.641-24813T>C
NM_001351110.2:c.*38+1336T>C
NM_001351834.2:c.7928-2A>G
LRG_135t1:c.7928-2A>G
LRG_135:g.116053A>G
NC_000011.9:g.108204611A>G
NM_000051.3:c.7928-2A>G

Links:

dbSNP: rs864622610

NCBI 1000 Genomes Browser:

rs864622610

Molecular consequence:

NM_001330368.2:c.641-24813T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+1336T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7928-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001351834.2:c.7928-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV002282333	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 22, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 29665859, 30287823, 16199547, 23807571, 25614872, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002282333

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 22, 2023)

germline

clinical testing

PubMed (6)
[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

Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

Renault AL, Mebirouk N, Fuhrmann L, Bataillon G, Cavaciuti E, Le Gal D, Girard E, Popova T, La Rosa P, Beauvallet J, Eon-Marchais S, Dondon MG, d'Enghien CD, Laugé A, Chemlali W, Raynal V, Labbé M, Bièche I, Baulande S, Bay JO, Berthet P, Caron O, et al.

Breast Cancer Res. 2018 Apr 17;20(1):28. doi: 10.1186/s13058-018-0951-9.

PubMed [citation]

PMID:: 29665859
PMCID:: PMC5905168

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002282333.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

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: 490718). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 29665859, 30287823). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 53 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).

#	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

ClinVar

Relating variation to medicine