NM_000075.4(CDK4):c.647G>A (p.Gly216Glu) AND Familial melanoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 5, 2024
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:: RCV001864628.4

Allele description [Variation Report for NM_000075.4(CDK4):c.647G>A (p.Gly216Glu)]

NM_000075.4(CDK4):c.647G>A (p.Gly216Glu)

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.647G>A (p.Gly216Glu)

HGVS:

NC_000012.12:g.57749490C>T
NG_007484.2:g.7892G>A
NM_000075.4:c.647G>AMANE SELECT
NM_001330168.2:c.*2200C>T
NM_001330169.2:c.*2200C>T
NM_005981.5:c.*2200C>TMANE SELECT
NP_000066.1:p.Gly216Glu
NP_000066.1:p.Gly216Glu
LRG_490t1:c.647G>A
LRG_490:g.7892G>A
LRG_490p1:p.Gly216Glu
NC_000012.11:g.58143273C>T
NM_000075.2:c.647G>A

Protein change:

G216E

Links:

dbSNP: rs1955206366

NCBI 1000 Genomes Browser:

rs1955206366

Molecular consequence:

NM_001330168.2:c.*2200C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001330169.2:c.*2200C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_005981.5:c.*2200C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000075.4:c.647G>A - 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

ADCYAP1R1 ADCYAP receptor type I [Bos taurus]
ADCYAP1R1 ADCYAP receptor type I [Bos taurus]
Gene ID:319095

Gene
319095[uid] AND (alive[prop]) (1)
Gene
srsf5a [Pundamilia nyererei]
srsf5a [Pundamilia nyererei]
Gene ID:102192163

Gene
Nicotiana silvestris mRNA for the small subunit of ribulose bisphosphate carboxy...
Nicotiana silvestris mRNA for the small subunit of ribulose bisphosphate carboxylase
gi|19759|emb|X01722.1|

Nucleotide
Plasmid pDS678/RBSII DNA sequence from patent EP0309746
Plasmid pDS678/RBSII DNA sequence from patent EP0309746
gi|14615|emb|A00781.1||pat|EP|03097

Nucleotide

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
SCV002141730	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 5, 2024)	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

SCV002141730

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 5, 2024)

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, SCV002141730.3

#	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 glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 216 of the CDK4 protein (p.Gly216Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1371732). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CDK4 protein function with a positive predictive value of 95%. 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

ClinVar

Relating variation to medicine