NM_000077.5(CDKN2A):c.339_340delinsCT (p.Pro114Ser) AND Familial melanoma

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 24, 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:: RCV001851778.13

Allele description

NM_000077.5(CDKN2A):c.339_340delinsCT (p.Pro114Ser)

Gene:

CDKN2A:cyclin dependent kinase inhibitor 2A [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

9p21.3

Genomic location:

Preferred name:

NM_000077.5(CDKN2A):c.339_340delinsCT (p.Pro114Ser)

Other names:

p.P114S:CCC>TCC

HGVS:

NC_000009.12:g.21971019_21971020delinsAG
NG_007485.1:g.28472_28473delGCinsCT
NG_007485.1:g.28472_28473delinsCT
NM_000077.5:c.339_340delinsCTMANE SELECT
NM_001195132.2:c.339_340delinsCT
NM_001363763.2:c.186_187delinsCT
NM_058195.4:c.382_383delinsCT
NM_058197.5:c.*262_*263delinsCT
NP_000068.1:p.Pro114Ser
NP_001182061.1:p.Pro114Ser
NP_001350692.1:p.Pro63Ser
NP_478102.2:p.Ala128Leu
LRG_11:g.28472_28473delinsCT
NC_000009.11:g.21971018_21971019delinsAG
NG_007485.1:g.28472_28473delGCinsCT
NM_000077.4:c.339_340delGCinsCT

Protein change:

A128L; LEU113LEU AND PRO114SER

Links:

OMIM: 600160.0017; dbSNP: rs387906410

NCBI 1000 Genomes Browser:

rs387906410

Molecular consequence:

NM_058197.5:c.*262_*263delinsCT - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000077.5:c.339_340delinsCT - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.339_340delinsCT - missense variant - [Sequence Ontology: SO:0001583]
NM_001363763.2:c.186_187delinsCT - missense variant - [Sequence Ontology: SO:0001583]
NM_058195.4:c.382_383delinsCT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial melanoma
Synonyms:: Hereditary melanoma; Hereditary cutaneous melanoma
Identifiers:: MONDO: MONDO:0018961; MedGen: C1512419

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002291656	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 24, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9053859, 19260062, 23190892, 24659262, 17492760, 17992122, 21462282, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002291656

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 24, 2022)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Point mutations can inactivate in vitro and in vivo activities of p16(INK4a)/CDKN2A in human glioma.

Arap W, Knudsen ES, Wang JY, Cavenee WK, Huang HJ.

Oncogene. 1997 Feb 6;14(5):603-9.

PubMed [citation]

PMID:: 9053859

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

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV002291656.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CDKN2A (p16INK4a) function (PMID: 9053859, 19260062, 23190892, 24659262). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 9424). This variant is also known as c.382_383delinsCT (p.Ala128Leu) in the CDKN2A (p14ARF) transcript. This missense change has been observed in individual(s) with melanoma (PMID: 17492760, 17992122, 21462282). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 114 of the CDKN2A (p16INK4a) protein (p.Pro114Ser). The CDKN2A gene encodes two different proteins, p16INK4a and p14ARF, which are translated from alternative transcripts with different open reading frames. Both transcripts have been analyzed. We report either the variant with the higher classification or default to the CDKN2A (p16INK4a) variant. This report therefore includes the details for the CDKN2A (p16INK4a) variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

ClinVar

Relating variation to medicine