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NM_000077.5(CDKN2A):c.52_57dup (p.Thr18_Ala19dup) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 22, 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:
RCV003165886.2

Allele description [Variation Report for NM_000077.5(CDKN2A):c.52_57dup (p.Thr18_Ala19dup)]

NM_000077.5(CDKN2A):c.52_57dup (p.Thr18_Ala19dup)

Gene:
CDKN2A:cyclin dependent kinase inhibitor 2A [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
9p21.3
Genomic location:
Preferred name:
NM_000077.5(CDKN2A):c.52_57dup (p.Thr18_Ala19dup)
HGVS:
  • NC_000009.12:g.21974775_21974780dup
  • NG_007485.1:g.24716_24721dup
  • NM_000077.5:c.52_57dupMANE SELECT
  • NM_001195132.2:c.52_57dup
  • NM_001363763.2:c.-3-3568_-3-3563dup
  • NM_058195.4:c.194-3568_194-3563dup
  • NM_058197.5:c.52_57dup
  • NP_000068.1:p.Thr18_Ala19dup
  • NP_000068.1:p.Thr18_Ala19dup
  • NP_001182061.1:p.Thr18_Ala19dup
  • NP_478104.2:p.Thr18_Ala19dup
  • LRG_11t1:c.52_57dup
  • LRG_11:g.24716_24721dup
  • LRG_11p1:p.Thr18_Ala19dup
  • NC_000009.11:g.21974769_21974770insGGCCGT
  • NC_000009.11:g.21974774_21974779dup
  • NM_000077.4:c.52_57dup
  • NM_000077.4:c.52_57dupACGGCC
Links:
dbSNP: rs1563892769
NCBI 1000 Genomes Browser:
rs1563892769
Molecular consequence:
  • NM_000077.5:c.52_57dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001195132.2:c.52_57dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_058197.5:c.52_57dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_001363763.2:c.-3-3568_-3-3563dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_058195.4:c.194-3568_194-3563dup - intron variant - [Sequence Ontology: SO:0001627]

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
SCV003860802Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Nov 22, 2022) 		germlineclinical testing

PubMed (5)
[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

Functional, structural, and genetic evaluation of 20 CDKN2A germ line mutations identified in melanoma-prone families or patients.

Kannengiesser C, Brookes S, del Arroyo AG, Pham D, Bombled J, Barrois M, Mauffret O, Avril MF, Chompret A, Lenoir GM, Sarasin A; French Hereditary Melanoma Study Group., Peters G, Bressac-de Paillerets B.

Hum Mutat. 2009 Apr;30(4):564-74. doi: 10.1002/humu.20845.

PubMed [citation]
PMID:
19260062

Familial melanoma: clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family.

Maubec E, Chaudru V, Mohamdi H, Blondel C, Margaritte-Jeannin P, Forget S, Corda E, Boitier F, Dalle S, Vabres P, Perrot JL, Lyonnet DS, Zattara H, Mansard S, Grange F, Leccia MT, Vincent-Fetita L, Martin L, Crickx B, Joly P, Thomas L; French Familial Melanoma Study Group., et al.

J Am Acad Dermatol. 2012 Dec;67(6):1257-64. doi: 10.1016/j.jaad.2012.05.014. Epub 2012 Jul 26.

PubMed [citation]
PMID:
22841127
See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV003860802.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The c.52_57dupACGGCC variant (also known as p.T18_A19dup), located in coding exon 1 of the CDKN2A gene, results from an in-frame duplication of ACGGCC at nucleotide positions 52 to 57. This results in the duplication of 2 extra residues (TA) between codons 18 and 19. This alteration has been detected in multiple familial melanoma and/or pancreatic cancer cohorts (Soufir N et al. Hum Mol Genet, 1998 Feb;7:209-16; Maubec E et al. J Am Acad Dermatol, 2012 Dec;67:1257-64; Taylor NJ et al. J Invest Dermatol, 2017 12;137:2606-2612; Schwartz M et al. Clin Genet, 2019 12;96:579-584). This alteration was found to be non-functional in a CDK4 binding assay (Kannengiesser C et al. Hum Mutat, 2009 Apr;30:564-74). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). These amino acid positions are not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024