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NM_000077.5(CDKN2A):c.-14C>T AND CDKN2A-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 17, 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:
RCV003947681.1

Allele description [Variation Report for NM_000077.5(CDKN2A):c.-14C>T]

NM_000077.5(CDKN2A):c.-14C>T

Genes:
LOC130001603:ATAC-STARR-seq lymphoblastoid silent region 19811 [Gene]
CDKN2A:cyclin dependent kinase inhibitor 2A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9p21.3
Genomic location:
Preferred name:
NM_000077.5(CDKN2A):c.-14C>T
HGVS:
  • NC_000009.12:g.21974841G>A
  • NG_007485.1:g.24651C>T
  • NM_000077.5:c.-14C>TMANE SELECT
  • NM_001195132.2:c.-14C>T
  • NM_001363763.2:c.-3-3633C>T
  • NM_058195.4:c.194-3633C>T
  • NM_058197.5:c.-14C>T
  • LRG_11t1:c.-14C>T
  • LRG_11:g.24651C>T
  • NC_000009.11:g.21974840G>A
  • NM_000077.3:c.-14C>T
  • NM_000077.4:c.-14C>T
  • NM_058195.3:c.194-3633C>T
Links:
dbSNP: rs764244718
NCBI 1000 Genomes Browser:
rs764244718
Molecular consequence:
  • NM_000077.5:c.-14C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001195132.2:c.-14C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_058197.5:c.-14C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001363763.2:c.-3-3633C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_058195.4:c.194-3633C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
CDKN2A-related disorder
Synonyms:
CDKN2A-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004762506PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 17, 2024) 		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 PreventionGenetics, part of Exact Sciences, SCV004762506.1

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

Description

The CDKN2A c.194-3633C>T variant is predicted to interfere with splicing. This variant occurs in the regulatory region of the alternative p16INK4A transcript for this gene (NM_000077.4:c.-14C>T). This variant has previously been reported in individuals with multiple cutaneous melanomas (Hashemi et al. 2000. PubMed ID: 11156381; Goldstein et al. 2008. PubMed ID: 18178632; Additional file 2 - Harland et al. 2014. PubMed ID: 25780468) and breast cancer (Supporting table 1 - Tung et al. 2014. PubMed ID: 25186627). However, in vitro studies indicated that this variant may not have a significance impact on CDKN2A mRNA translation (Andreotti et al. 2016. PubMed ID: 26581427). In the gnomAD public population database this variant has been reported in up to ~0.046% of alleles in a subpopulation and has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/221032/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: May 26, 2024