NM_000077.5(CDKN2A):c.4G>C (p.Glu2Gln) AND Familial melanoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 2018
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:: RCV000470551.7

Allele description [Variation Report for NM_000077.5(CDKN2A):c.4G>C (p.Glu2Gln)]

NM_000077.5(CDKN2A):c.4G>C (p.Glu2Gln)

Genes:

LOC130001603:ATAC-STARR-seq lymphoblastoid silent region 19811 [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.4G>C (p.Glu2Gln)

HGVS:

NC_000009.12:g.21974824C>G
NG_007485.1:g.24668G>C
NM_000077.5:c.4G>CMANE SELECT
NM_001195132.2:c.4G>C
NM_001363763.2:c.-3-3616G>C
NM_058195.4:c.194-3616G>C
NM_058197.5:c.4G>C
NP_000068.1:p.Glu2Gln
NP_000068.1:p.Glu2Gln
NP_001182061.1:p.Glu2Gln
NP_478104.2:p.Glu2Gln
LRG_11t1:c.4G>C
LRG_11:g.24668G>C
LRG_11p1:p.Glu2Gln
NC_000009.11:g.21974823C>G
NM_000077.4:c.4G>C

Protein change:

E2Q

Links:

dbSNP: rs1060501273

NCBI 1000 Genomes Browser:

rs1060501273

Molecular consequence:

NM_001363763.2:c.-3-3616G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_058195.4:c.194-3616G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000077.5:c.4G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.4G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_058197.5:c.4G>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
SCV000545547	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2018)	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

SCV000545547

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2018)

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 Invitae, SCV000545547.6

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

Description

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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CDKN2A-related disease. This sequence change replaces glutamic acid with glutamine at codon 2 of the CDKN2A protein (p.Glu2Gln). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and glutamine.

#	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 1, 2024

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