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NM_000051.4(ATM):c.6807G>A (p.Gln2269=) AND Ataxia-telangiectasia syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 19, 2024
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:
RCV000122879.15

Allele description [Variation Report for NM_000051.4(ATM):c.6807G>A (p.Gln2269=)]

NM_000051.4(ATM):c.6807G>A (p.Gln2269=)

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.6807G>A (p.Gln2269=)
Other names:
NM_000051.4(ATM):c.6807G>A; p.Gln2269=
HGVS:
  • NC_000011.10:g.108325544G>A
  • NG_009830.1:g.107713G>A
  • NG_054724.1:g.149289C>T
  • NM_000051.4:c.6807G>AMANE SELECT
  • NM_001330368.2:c.641-16473C>T
  • NM_001351110.2:c.*38+9676C>T
  • NM_001351834.2:c.6807G>A
  • NP_000042.3:p.Gln2269=
  • NP_000042.3:p.Gln2269=
  • NP_001338763.1:p.Gln2269=
  • LRG_135t1:c.6807G>A
  • LRG_135:g.107713G>A
  • LRG_135p1:p.Gln2269=
  • NC_000011.9:g.108196271G>A
  • NM_000051.3:c.6807G>A
Links:
dbSNP: rs587780638
NCBI 1000 Genomes Browser:
rs587780638
Molecular consequence:
  • NM_001330368.2:c.641-16473C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+9676C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.6807G>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001351834.2:c.6807G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000166137Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 19, 2024)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000166137.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects codon 2269 of the ATM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with breast cancer and/or clinical features of ataxia-telangiectasia (PMID: 30549301; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 135775). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 46 and introduces a premature termination codon (PMID: 30549301; Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 8, 2025