NM_000075.4(CDK4):c.763C>T (p.Arg255Cys) AND Melanoma, cutaneous malignant, susceptibility to, 3

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: May 28, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000988867.7

Allele description [Variation Report for NM_000075.4(CDK4):c.763C>T (p.Arg255Cys)]

NM_000075.4(CDK4):c.763C>T (p.Arg255Cys)

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.763C>T (p.Arg255Cys)

HGVS:

NC_000012.12:g.57749238G>A
NG_007484.2:g.8144C>T
NM_000075.4:c.763C>TMANE SELECT
NM_001330168.2:c.*1948G>A
NM_001330169.2:c.*1948G>A
NM_005981.5:c.*1948G>AMANE SELECT
NP_000066.1:p.Arg255Cys
LRG_490:g.8144C>T
NC_000012.11:g.58143021G>A
NM_000075.3:c.763C>T

Protein change:

R255C

Links:

dbSNP: rs587778188

NCBI 1000 Genomes Browser:

rs587778188

Molecular consequence:

NM_001330168.2:c.*1948G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001330169.2:c.*1948G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_005981.5:c.*1948G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000075.4:c.763C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Melanoma, cutaneous malignant, susceptibility to, 3
Synonyms:: Cutaneous malignant melanoma 3
Identifiers:: MONDO: MONDO:0012183; MedGen: C1836892; Orphanet: 618; OMIM: 609048

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001138761	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001272969	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 12, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001138761

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV001272969

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 12, 2018)

germline

clinical testing

Citation Link

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Mendelics, SCV001138761.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV001272969.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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: May 7, 2024

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