NM_000075.4(CDK4):c.848G>C (p.Arg283Pro) AND Familial melanoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 13, 2020
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:: RCV001363026.7

Allele description [Variation Report for NM_000075.4(CDK4):c.848G>C (p.Arg283Pro)]

NM_000075.4(CDK4):c.848G>C (p.Arg283Pro)

Genes:

CDK4:cyclin dependent kinase 4 [Gene - OMIM - HGNC]
TSPAN31:tetraspanin 31 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q14.1

Genomic location:

Preferred name:

NM_000075.4(CDK4):c.848G>C (p.Arg283Pro)

HGVS:

NC_000012.12:g.57748589C>G
NG_007484.2:g.8793G>C
NM_000075.4:c.848G>CMANE SELECT
NM_001330168.2:c.*1299C>G
NM_001330169.2:c.*1299C>G
NM_005981.5:c.*1299C>GMANE SELECT
NP_000066.1:p.Arg283Pro
NP_000066.1:p.Arg283Pro
LRG_490t1:c.848G>C
LRG_490:g.8793G>C
LRG_490p1:p.Arg283Pro
NC_000012.11:g.58142372C>G
NM_000075.2:c.848G>C

Protein change:

R283P

Links:

dbSNP: rs1595107806

NCBI 1000 Genomes Browser:

rs1595107806

Molecular consequence:

NM_001330168.2:c.*1299C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001330169.2:c.*1299C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_005981.5:c.*1299C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000075.4:c.848G>C - 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
SCV001559104	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2020)	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

SCV001559104

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2020)

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, SCV001559104.4

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

Description

This sequence change replaces arginine with proline at codon 283 of the CDK4 protein (p.Arg283Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDK4-related conditions.

#	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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