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NM_000077.5(CDKN2A):c.156G>C (p.Met52Ile) AND Familial melanoma

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 30, 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:
RCV003036648.2

Allele description [Variation Report for NM_000077.5(CDKN2A):c.156G>C (p.Met52Ile)]

NM_000077.5(CDKN2A):c.156G>C (p.Met52Ile)

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.156G>C (p.Met52Ile)
HGVS:
  • NC_000009.12:g.21971203C>G
  • NG_007485.1:g.28289G>C
  • NM_000077.5:c.156G>CMANE SELECT
  • NM_001195132.2:c.156G>C
  • NM_001363763.2:c.3G>C
  • NM_058195.4:c.199G>C
  • NM_058197.5:c.*79G>C
  • NP_000068.1:p.Met52Ile
  • NP_000068.1:p.Met52Ile
  • NP_001182061.1:p.Met52Ile
  • NP_001350692.1:p.Met1Ile
  • NP_478102.2:p.Asp67His
  • NP_478102.2:p.Asp67His
  • LRG_11t1:c.156G>C
  • LRG_11t2:c.199G>C
  • LRG_11:g.28289G>C
  • LRG_11p1:p.Met52Ile
  • LRG_11p2:p.Asp67His
  • NC_000009.11:g.21971202C>G
  • NM_000077.4:c.156G>C
  • NM_058195.3:c.199G>C
Protein change:
D67H
Molecular consequence:
  • NM_058197.5:c.*79G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001363763.2:c.3G>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_000077.5:c.156G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195132.2:c.156G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363763.2:c.3G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_058195.4:c.199G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003351764Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 30, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV003351764.3

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. 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. This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 52 of the CDKN2A (p16INK4a) protein (p.Met52Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. This variant is also known as c.199G>C (p.Asp67His) in CDKN2A (p14ARF) transcript.

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

Last Updated: May 1, 2024