NM_000077.5(CDKN2A):c.286G>T (p.Val96Leu) AND Familial melanoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 26, 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:: RCV003015156.3

Allele description [Variation Report for NM_000077.5(CDKN2A):c.286G>T (p.Val96Leu)]

NM_000077.5(CDKN2A):c.286G>T (p.Val96Leu)

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.286G>T (p.Val96Leu)

HGVS:

NC_000009.12:g.21971073C>A
NG_007485.1:g.28419G>T
NM_000077.5:c.286G>TMANE SELECT
NM_001195132.2:c.286G>T
NM_001363763.2:c.133G>T
NM_058195.4:c.329G>T
NM_058197.5:c.*209G>T
NP_000068.1:p.Val96Leu
NP_000068.1:p.Val96Leu
NP_001182061.1:p.Val96Leu
NP_001350692.1:p.Val45Leu
NP_478102.2:p.Gly110Val
NP_478102.2:p.Gly110Val
LRG_11t1:c.286G>T
LRG_11t2:c.329G>T
LRG_11:g.28419G>T
LRG_11p1:p.Val96Leu
LRG_11p2:p.Gly110Val
NC_000009.11:g.21971072C>A
NM_000077.4:c.286G>T
NM_058195.3:c.329G>T

Protein change:

G110V

Molecular consequence:

NM_058197.5:c.*209G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000077.5:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363763.2:c.133G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_058195.4:c.329G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003322910	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 26, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003322910

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 26, 2022)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003322910.2

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

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant is also known as c.329G>T (p.Gly110Val) in CDKN2A (p14ARF) NM_058195.3. This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 96 of the CDKN2A (p16INK4a) protein (p.Val96Leu). 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 29, 2024

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