NM_000075.4(CDK4):c.222_223delinsCT (p.Met75Leu) AND Hereditary melanoma

Clinical significance:Uncertain significance (Last evaluated: Dec 26, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001052819.2

Allele description [Variation Report for NM_000075.4(CDK4):c.222_223delinsCT (p.Met75Leu)]

NM_000075.4(CDK4):c.222_223delinsCT (p.Met75Leu)

Gene:
CDK4:cyclin dependent kinase 4 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
12q14.1
Genomic location:
Preferred name:
NM_000075.4(CDK4):c.222_223delinsCT (p.Met75Leu)
HGVS:
  • NC_000012.12:g.57751338_57751339delinsAG
  • NG_007484.2:g.6043_6044delinsCT
  • NM_000075.4:c.222_223delinsCTMANE SELECT
  • NP_000066.1:p.Met75Leu
  • LRG_490:g.6043_6044delinsCT
  • NC_000012.11:g.58145121_58145122delinsAG
  • NM_000075.3:c.222_223delinsCT
Protein change:
M75L
Molecular consequence:
  • NM_000075.4:c.222_223delinsCT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001217048Invitaecriteria provided, single submitter
Uncertain significance
(Dec 26, 2019)
germlineclinical testing

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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001217048.2

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

Description

This sequence change replaces methionine with leucine at codon 75 of the CDK4 protein (p.Met75Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDK4-related conditions. 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: Tolerated; PolyPhen-2: Not Available; 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.

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

Last Updated: Oct 7, 2021

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