NM_000077.5(CDKN2A):c.116A>G (p.Asn39Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 21, 2023
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:: RCV004070135.1

Allele description [Variation Report for NM_000077.5(CDKN2A):c.116A>G (p.Asn39Ser)]

NM_000077.5(CDKN2A):c.116A>G (p.Asn39Ser)

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.116A>G (p.Asn39Ser)

HGVS:

NC_000009.12:g.21974712T>C
NG_007485.1:g.24780A>G
NM_000077.5:c.116A>GMANE SELECT
NM_001195132.2:c.116A>G
NM_001363763.2:c.-3-3504A>G
NM_058195.4:c.194-3504A>G
NM_058197.5:c.116A>G
NP_000068.1:p.Asn39Ser
NP_000068.1:p.Asn39Ser
NP_001182061.1:p.Asn39Ser
NP_478104.2:p.Asn39Ser
LRG_11t1:c.116A>G
LRG_11:g.24780A>G
LRG_11p1:p.Asn39Ser
NC_000009.11:g.21974711T>C
NM_000077.4:c.116A>G

Protein change:

N39S

Molecular consequence:

NM_001363763.2:c.-3-3504A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_058195.4:c.194-3504A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000077.5:c.116A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.116A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_058197.5:c.116A>G - 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
SCV005032101	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 21, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25064638, 30038052 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005032101

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 21, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Increased prevalence of lung, breast, and pancreatic cancers in addition to melanoma risk in families bearing the cyclin-dependent kinase inhibitor 2A mutation: implications for genetic counseling.

Potrony M, Puig-Butillé JA, Aguilera P, Badenas C, Carrera C, Malvehy J, Puig S.

J Am Acad Dermatol. 2014 Nov;71(5):888-95. doi: 10.1016/j.jaad.2014.06.036. Epub 2014 Jul 24.

PubMed [citation]

PMID:: 25064638
PMCID:: PMC4250348

CDKN2A Germline Rare Coding Variants and Risk of Pancreatic Cancer in Minority Populations.

McWilliams RR, Wieben ED, Chaffee KG, Antwi SO, Raskin L, Olopade OI, Li D, Highsmith WE Jr, Colon-Otero G, Khanna LG, Permuth JB, Olson JE, Frucht H, Genkinger J, Zheng W, Blot WJ, Wu L, Almada LL, Fernandez-Zapico ME, Sicotte H, Pedersen KS, Petersen GM.

Cancer Epidemiol Biomarkers Prev. 2018 Nov;27(11):1364-1370. doi: 10.1158/1055-9965.EPI-17-1065. Epub 2018 Jul 23.

PubMed [citation]

PMID:: 30038052
PMCID:: PMC6214745

Details of each submission

From Ambry Genetics, SCV005032101.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.N39S variant (also known as c.116A>G), located in coding exon 1 of the CDKN2A gene, results from an A to G substitution at nucleotide position 116. The asparagine at codon 39 is replaced by serine, an amino acid with highly similar properties. In a study of 236 sporadic multiple primary melanoma patients and 466 familial melanoma patients belonging to 330 high-risk melanoma-prone families, this alteration was identified in one melanoma-prone family (Potrony M et al. J Am Acad Dermatol, 2014 Nov;71:888-95). This alteration was not identified in 220 African American pancreatic cancer cases and was identified in 1/900 non-cancer African American controls (McWilliams RR et al. Cancer Epidemiol Biomarkers Prev, 2018 Nov;27:1364-1370). 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