NM_000051.4(ATM):c.2838+6T>G AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 30, 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:: RCV003500003.2

Allele description [Variation Report for NM_000051.4(ATM):c.2838+6T>G]

NM_000051.4(ATM):c.2838+6T>G

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.2838+6T>G

HGVS:

NC_000011.10:g.108268615T>G
NG_009830.1:g.50784T>G
NM_000051.4:c.2838+6T>GMANE SELECT
NM_001351834.2:c.2838+6T>G
LRG_135:g.50784T>G
NC_000011.9:g.108139342T>G

Molecular consequence:

NM_000051.4:c.2838+6T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351834.2:c.2838+6T>G - 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

Recent activity

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5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase 1-like [Cynara cardun...
5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase 1-like [Cynara cardunculus var. scolymus]
gi|1389761811|ref|XP_024984512.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004312165	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 30, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 33098801, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004312165

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 30, 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

Monogenic variants in dystonia: an exome-wide sequencing study.

Zech M, Jech R, Boesch S, Škorvánek M, Weber S, Wagner M, Zhao C, Jochim A, Necpál J, Dincer Y, Vill K, Distelmaier F, Stoklosa M, Krenn M, Grunwald S, Bock-Bierbaum T, Fečíková A, Havránková P, Roth J, Příhodová I, Adamovičová M, Ulmanová O, et al.

Lancet Neurol. 2020 Nov;19(11):908-918. doi: 10.1016/S1474-4422(20)30312-4.

PubMed [citation]

PMID:: 33098801
PMCID:: PMC8246240

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004312165.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the c.2838+6 nucleotide in the ATM gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 33098801). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 18 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. It affects a nucleotide within the consensus splice site.

#	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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