NM_000077.5(CDKN2A):c.262G>C (p.Glu88Gln) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 8, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002256493.3

Allele description [Variation Report for NM_000077.5(CDKN2A):c.262G>C (p.Glu88Gln)]

NM_000077.5(CDKN2A):c.262G>C (p.Glu88Gln)

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.262G>C (p.Glu88Gln)

HGVS:

NC_000009.12:g.21971097C>G
NG_007485.1:g.28395G>C
NM_000077.5:c.262G>CMANE SELECT
NM_001195132.2:c.262G>C
NM_001363763.2:c.109G>C
NM_058195.4:c.305G>C
NM_058197.5:c.*185G>C
NP_000068.1:p.Glu88Gln
NP_000068.1:p.Glu88Gln
NP_001182061.1:p.Glu88Gln
NP_001350692.1:p.Glu37Gln
NP_478102.2:p.Gly102Ala
LRG_11t1:c.262G>C
LRG_11:g.28395G>C
LRG_11p1:p.Glu88Gln
NC_000009.11:g.21971096C>G
NM_000077.4:c.262G>C

Protein change:

E37Q

Links:

dbSNP: rs121913384

NCBI 1000 Genomes Browser:

rs121913384

Molecular consequence:

NM_058197.5:c.*185G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000077.5:c.262G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.262G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363763.2:c.109G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_058195.4:c.305G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

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
SCV002534323	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Feb 14, 2022)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV005032159	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 8, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002534323

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Feb 14, 2022)

germline

curation

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

Citation Link,

SCV005032159

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 8, 2024)

germline

clinical testing

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

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, curation

Citations

PubMed

Alterations in CDKN2A locus as potential indicator of melanoma predisposition in relatives of non-familial melanoma cases.

Levanat S, Situm M, Crnić I, Marasović D, Puizina-Ivić N, Pokupcić N, Musani V, Komar A, Kubat M, Furac I, Karija-Vlahović M, Krizanac S.

Croat Med J. 2003 Aug;44(4):418-24.

PubMed [citation]

PMID:: 12950144

Details of each submission

From Sema4, Sema4, SCV002534323.1

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

#	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

From Ambry Genetics, SCV005032159.1

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

Description

The p.E88Q variant (also known as c.262G>C), located in coding exon 2 of the CDKN2A gene, results from a G to C substitution at nucleotide position 262. The glutamic acid at codon 88 is replaced by glutamine, an amino acid with highly similar properties. This alteration was detected in a proband with melanoma as well as in an unaffected family member. The affected proband was also found to have a pathogenic frameshift mutation in the CDKN2A gene that was not present in the unaffected relative (Levanat S et al. Croat Med J, 2003 Aug;44:418-24). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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