NM_000077.5(CDKN2A):c.-14C>T AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jun 18, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000579472.6

Allele description [Variation Report for NM_000077.5(CDKN2A):c.-14C>T]

NM_000077.5(CDKN2A):c.-14C>T

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.-14C>T

HGVS:

NC_000009.12:g.21974841G>A
NG_007485.1:g.24651C>T
NM_000077.5:c.-14C>TMANE SELECT
NM_001195132.2:c.-14C>T
NM_001363763.2:c.-3-3633C>T
NM_058195.4:c.194-3633C>T
NM_058197.5:c.-14C>T
LRG_11t1:c.-14C>T
LRG_11:g.24651C>T
NC_000009.11:g.21974840G>A
NM_000077.3:c.-14C>T
NM_000077.4:c.-14C>T
NM_058195.3:c.194-3633C>T

Links:

dbSNP: rs764244718

NCBI 1000 Genomes Browser:

rs764244718

Molecular consequence:

NM_000077.5:c.-14C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001195132.2:c.-14C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_058197.5:c.-14C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001363763.2:c.-3-3633C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_058195.4:c.194-3633C>T - intron variant - [Sequence Ontology: SO:0001627]

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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PM1-HT0350-070100-006-b02 HT0350 Homo sapiens cDNA, mRNA sequence
PM1-HT0350-070100-006-b02 HT0350 Homo sapiens cDNA, mRNA sequence
gi|7254879|gnl|dbEST|4012352|gb|AW5 .1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000684500	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Aug 8, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002534308	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Jun 18, 2021)	germline	curation	PubMed (6) [See all records that cite these PMIDs] 26581427, 25780468, 18178632, 11156381, 25186627, 21150883 Citation Link,
SCV004848957	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 25, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000684500

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Aug 8, 2016)

germline

clinical testing

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

SCV002534308

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Jun 18, 2021)

germline

curation

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV004848957

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 25, 2015)

germline

clinical testing

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

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

The CDKN2A/p16(INK) (4a) 5'UTR sequence and translational regulation: impact of novel variants predisposing to melanoma.

Andreotti V, Bisio A, Bressac-de Paillerets B, Harland M, Cabaret O, Newton-Bishop J, Pastorino L, Bruno W, Bertorelli R, De Sanctis V, Provenzani A, Menin C, Fronza G, Queirolo P, Spitale RC, Bianchi-Scarrà G, Inga A, Ghiorzo P.

Pigment Cell Melanoma Res. 2016 Mar;29(2):210-21. doi: 10.1111/pcmr.12444. Epub 2015 Dec 17.

PubMed [citation]

PMID:: 26581427

See all PubMed Citations (7)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000684500.2

#	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 Sema4, Sema4, SCV002534308.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (6)

#	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, SCV004848957.1

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

Description

The c.-14C>T alteration is located in the 5' untranslated region (5'UTR) of the CDKN2A gene. This alteration consists of a C to T substitution nucleotides upstream from the first translated codon. Based on insufficient or conflicting evidence, 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: May 26, 2024

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