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NM_000077.5(CDKN2A):c.188T>C (p.Leu63Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 18, 2022
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:
RCV002406961.2

Allele description [Variation Report for NM_000077.5(CDKN2A):c.188T>C (p.Leu63Pro)]

NM_000077.5(CDKN2A):c.188T>C (p.Leu63Pro)

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.188T>C (p.Leu63Pro)
HGVS:
  • NC_000009.12:g.21971171A>G
  • NG_007485.1:g.28321T>C
  • NM_000077.5:c.188T>CMANE SELECT
  • NM_001195132.2:c.188T>C
  • NM_001363763.2:c.35T>C
  • NM_058195.4:c.231T>C
  • NM_058197.5:c.*111T>C
  • NP_000068.1:p.Leu63Pro
  • NP_001182061.1:p.Leu63Pro
  • NP_001350692.1:p.Leu12Pro
  • NP_478102.2:p.Ala77=
  • LRG_11t1:c.188T>C
  • LRG_11:g.28321T>C
  • NC_000009.11:g.21971170A>G
  • NM_000077.4:c.188T>C
Protein change:
L12P
Links:
dbSNP: rs2131096164
NCBI 1000 Genomes Browser:
rs2131096164
Molecular consequence:
  • NM_058197.5:c.*111T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000077.5:c.188T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195132.2:c.188T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363763.2:c.35T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_058195.4:c.231T>C - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV002722492Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Apr 18, 2022) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents.

Goldstein AM, Chan M, Harland M, Hayward NK, Demenais F, Bishop DT, Azizi E, Bergman W, Bianchi-Scarra G, Bruno W, Calista D, Albright LA, Chaudru V, Chompret A, Cuellar F, Elder DE, Ghiorzo P, Gillanders EM, Gruis NA, Hansson J, Hogg D, Holland EA, et al.

J Med Genet. 2007 Feb;44(2):99-106. Epub 2006 Aug 11.

PubMed [citation]
PMID:
16905682
PMCID:
PMC2598064

Subtype assignment and phylogenetic analysis of HIV type 1 strains in patients from Swaziland.

Dehò L, Walwema R, Cappelletti A, Sukati H, Sibandze D, Almaviva M, Buttò S, Ensoli B, Galli M, Balotta C.

AIDS Res Hum Retroviruses. 2008 Feb;24(2):323-5. doi: 10.1089/aid.2007.0233.

PubMed [citation]
PMID:
18257688
See all PubMed Citations (12)

Details of each submission

From Ambry Genetics, SCV002722492.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

The p.L63P pathogenic mutation (also known as c.188T>C), located in coding exon 2 of the CDKN2A gene, results from a T to C substitution at nucleotide position 188. The leucine at codon 63 is replaced by proline, an amino acid with similar properties. This alteration has been reported in a family with more than three patients with melanoma (Goldstein AM et al. J. Med. Genet. 2007 Feb;44:99-106; Harland M et al. Hered. Cancer Clin. Pract. 2014 Nov;12:20). This alteration has been observed in individuals who have a personal or family history that is consistent with CDKN2A-associated disease (Ambry internal data). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Ambry internal data; Byeon IJ et al. Mol. Cell 1998 Feb;1(3):421-31). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024