NM_000077.5(CDKN2A):c.35C>A (p.Ser12Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 9, 2021
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:: RCV000775634.4

Allele description [Variation Report for NM_000077.5(CDKN2A):c.35C>A (p.Ser12Ter)]

NM_000077.5(CDKN2A):c.35C>A (p.Ser12Ter)

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.35C>A (p.Ser12Ter)

HGVS:

NC_000009.12:g.21974793G>T
NG_007485.1:g.24699C>A
NM_000077.5:c.35C>AMANE SELECT
NM_001195132.2:c.35C>A
NM_001363763.2:c.-3-3585C>A
NM_058195.4:c.194-3585C>A
NM_058197.5:c.35C>A
NP_000068.1:p.Ser12Ter
NP_000068.1:p.Ser12Ter
NP_001182061.1:p.Ser12Ter
NP_478104.2:p.Ser12Ter
LRG_11t1:c.35C>A
LRG_11:g.24699C>A
LRG_11p1:p.Ser12Ter
NC_000009.11:g.21974792G>T
NM_000077.4:c.35C>A

Protein change:

S12*

Links:

dbSNP: rs141798398

NCBI 1000 Genomes Browser:

rs141798398

Molecular consequence:

NM_001363763.2:c.-3-3585C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_058195.4:c.194-3585C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000077.5:c.35C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001195132.2:c.35C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_058197.5:c.35C>A - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000909998	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 5, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002617379	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 9, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 14722037, 27083775, 28830827 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000909998

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 5, 2018)

germline

clinical testing

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

SCV002617379

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 9, 2021)

germline

clinical testing

PubMed (3)
[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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

BRAF gene is somatically mutated but does not make a major contribution to malignant melanoma susceptibility: the Italian Melanoma Intergroup Study.

Casula M, Colombino M, Satta MP, Cossu A, Ascierto PA, Bianchi-Scarrà G, Castiglia D, Budroni M, Rozzo C, Manca A, Lissia A, Carboni A, Petretto E, Satriano SM, Botti G, Mantelli M, Ghiorzo P, Stratton MR, Tanda F, Palmieri G; Italian Melanoma Intergroup Study..

J Clin Oncol. 2004 Jan 15;22(2):286-92. Erratum in: J Clin Oncol. 2005 Feb 1;23(4):936.

PubMed [citation]

PMID:: 14722037

See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000909998.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	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, SCV002617379.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.S12* pathogenic mutation (also known as c.35C>A), located in coding exon 1 of the CDKN2A gene, results from a C to A substitution at nucleotide position 35. This changes the amino acid from a serine to a stop codon within coding exon 1. This alteration has been reported in patients affected with melanoma (Casula M et al. J Clin Oncol, 2004 Jan;22:286-92; Seifert BA et al. Clin Cancer Res, 2016 Aug;22:4087-4094; Taylor NJ et al. J Invest Dermatol, 2017 12;137:2606-2612). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: Oct 13, 2024

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