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NM_000051.4(ATM):c.7928-2A>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 15, 2020
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:
RCV001186440.12

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

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

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>C
HGVS:
  • NC_000011.10:g.108333884A>C
  • NG_009830.1:g.116053A>C
  • NG_054724.1:g.140949T>G
  • NM_000051.4:c.7928-2A>CMANE SELECT
  • NM_001330368.2:c.641-24813T>G
  • NM_001351110.2:c.*38+1336T>G
  • NM_001351834.2:c.7928-2A>C
  • LRG_135t1:c.7928-2A>C
  • LRG_135:g.116053A>C
  • NC_000011.9:g.108204611A>C
  • NM_000051.3:c.7928-2A>C
Links:
dbSNP: rs864622610
NCBI 1000 Genomes Browser:
rs864622610
Molecular consequence:
  • NM_001330368.2:c.641-24813T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+1336T>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.7928-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001351834.2:c.7928-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001352843Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 15, 2020) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001352843.2

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

Description

This variant causes an A>C nucleotide substitution at the -2 position of intron 53 of the ATM gene. While this variant is predicted to disrupt the intron 53 splice acceptor site, there is an in-frame cryptic splice site that is predicted to cause the deletion of the first 3 bases of exon 54. To our knowledge, RNA and functional studies have not been performed for this variant. This variant has been reported in an individual affected with early-onset breast cancer from an ataxia-telangiectasia (A-T) family (PMID: 29665859). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Two other canonical splice acceptor site variants in this intron also have been described in the literature. ATM c.7928-2A>G was observed in a breast cancer case-control study in one control and absent in the cancer cases (PMID: 19781682) and ATM c.7928-1G>A was observed in cis with c.3111delT and in trans with c.5441T>A (p.Trp1814X) in an A-T affected individual (PMID: 17910737). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 10, 2024