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NM_000051.4(ATM):c.5763-1056G>A AND Ataxia-telangiectasia syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 22, 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:
RCV003607435.2

Allele description [Variation Report for NM_000051.4(ATM):c.5763-1056G>A]

NM_000051.4(ATM):c.5763-1056G>A

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.5763-1056G>A
HGVS:
  • NC_000011.10:g.108309104G>A
  • NG_009830.1:g.91273G>A
  • NG_054724.1:g.165729C>T
  • NM_000051.4:c.5763-1056G>AMANE SELECT
  • NM_001330368.2:c.641-33C>T
  • NM_001351110.2:c.*39-33C>T
  • NM_001351834.2:c.5763-1056G>A
  • LRG_135t1:c.5763-1056G>A
  • LRG_135:g.91273G>A
  • NC_000011.9:g.108179831G>A
  • NM_000051.3:c.5763-1056G>A
Links:
dbSNP: rs1325461375
NCBI 1000 Genomes Browser:
rs1325461375
Molecular consequence:
  • NM_000051.4:c.5763-1056G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001330368.2:c.641-33C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*39-33C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351834.2:c.5763-1056G>A - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004554147Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jan 22, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes.

Dragoš VŠ, Strojnik K, Klančar G, Škerl P, Stegel V, Blatnik A, Banjac M, Krajc M, Novaković S.

Int J Mol Sci. 2022 Jul 4;23(13). doi:pii: 7446. 10.3390/ijms23137446.

PubMed [citation]
PMID:
35806449
PMCID:
PMC9267136

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004554147.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change falls in intron 38 of the ATM gene. It does not directly 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. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has been observed in individual(s) with breast cancer (PMID: 35806449). ClinVar contains an entry for this variant (Variation ID: 1696413). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 35806449; Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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.

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

Last Updated: Nov 3, 2024