NM_000077.5(CDKN2A):c.107C>T (p.Ala36Val) AND Familial melanoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 26, 2023
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:: RCV001858283.6

Allele description [Variation Report for NM_000077.5(CDKN2A):c.107C>T (p.Ala36Val)]

NM_000077.5(CDKN2A):c.107C>T (p.Ala36Val)

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.107C>T (p.Ala36Val)

HGVS:

NC_000009.12:g.21974721G>A
NG_007485.1:g.24771C>T
NM_000077.5:c.107C>TMANE SELECT
NM_001195132.2:c.107C>T
NM_001363763.2:c.-3-3513C>T
NM_058195.4:c.194-3513C>T
NM_058197.5:c.107C>T
NP_000068.1:p.Ala36Val
NP_000068.1:p.Ala36Val
NP_001182061.1:p.Ala36Val
NP_478104.2:p.Ala36Val
LRG_11t1:c.107C>T
LRG_11:g.24771C>T
LRG_11p1:p.Ala36Val
NC_000009.11:g.21974720G>A
NM_000077.4:c.107C>T

Protein change:

A36V

Links:

dbSNP: rs200382984

NCBI 1000 Genomes Browser:

rs200382984

Molecular consequence:

NM_001363763.2:c.-3-3513C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_058195.4:c.194-3513C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000077.5:c.107C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.107C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_058197.5:c.107C>T - 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

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Mus musculus reticulon 4 (Rtn4), transcript variant 4, mRNA
Mus musculus reticulon 4 (Rtn4), transcript variant 4, mRNA
gi|142374254|ref|NM_024226.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002291585	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26104880, 34369425, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002291585

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 26, 2023)

germline

clinical testing

PubMed (3)
[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

Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children.

Xu H, Zhang H, Yang W, Yadav R, Morrison AC, Qian M, Devidas M, Liu Y, Perez-Andreu V, Zhao X, Gastier-Foster JM, Lupo PJ, Neale G, Raetz E, Larsen E, Bowman WP, Carroll WL, Winick N, Williams R, Hansen T, Holm JC, Mardis E, et al.

Nat Commun. 2015 Jun 24;6:7553. doi: 10.1038/ncomms8553.

PubMed [citation]

PMID:: 26104880
PMCID:: PMC4544058

The functional role of inherited CDKN2A variants in childhood acute lymphoblastic leukemia.

Li C, Zhao X, He Y, Li Z, Qian J, Zhang L, Ye Q, Qiu F, Lian P, Qian M, Zhang H.

Pharmacogenet Genomics. 2022 Feb 1;32(2):43-50. doi: 10.1097/FPC.0000000000000451.

PubMed [citation]

PMID:: 34369425
PMCID:: PMC8694244

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002291585.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 36 of the CDKN2A (p16INK4a) protein (p.Ala36Val). This variant is present in population databases (no rsID available, gnomAD 0.001%). This missense change has been observed in individual(s) with childhood leukemia (PMID: 26104880). ClinVar contains an entry for this variant (Variation ID: 483324). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects CDKN2A (p16INK4a) function (PMID: 34369425). 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.

#	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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