NM_000077.5(CDKN2A):c.212A>G (p.Asn71Ser) AND Familial melanoma

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 10, 2024
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:: RCV000692301.10

Allele description [Variation Report for NM_000077.5(CDKN2A):c.212A>G (p.Asn71Ser)]

NM_000077.5(CDKN2A):c.212A>G (p.Asn71Ser)

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.212A>G (p.Asn71Ser)

HGVS:

NC_000009.12:g.21971147T>C
NG_007485.1:g.28345A>G
NM_000077.5:c.212A>GMANE SELECT
NM_001195132.2:c.212A>G
NM_001363763.2:c.59A>G
NM_058195.4:c.255A>G
NM_058197.5:c.*135A>G
NP_000068.1:p.Asn71Ser
NP_000068.1:p.Asn71Ser
NP_001182061.1:p.Asn71Ser
NP_001350692.1:p.Asn20Ser
NP_478102.2:p.Gln85=
LRG_11t1:c.212A>G
LRG_11:g.28345A>G
LRG_11p1:p.Asn71Ser
NC_000009.11:g.21971146T>C
NM_000077.4:c.212A>G

Protein change:

N20S

Links:

dbSNP: rs559848002

NCBI 1000 Genomes Browser:

rs559848002

Molecular consequence:

NM_058197.5:c.*135A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000077.5:c.212A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.212A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001363763.2:c.59A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_058195.4:c.255A>G - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Familial melanoma
Synonyms:: Hereditary melanoma; Hereditary cutaneous melanoma
Identifiers:: MONDO: MONDO:0018961; MedGen: C1512419

Recent activity

Clear Turn Off Turn On

Sds24p [Saccharomyces cerevisiae S288C]
Sds24p [Saccharomyces cerevisiae S288C]
gi|6319691|ref|NP_009773.1|

Protein
Enterobacteria phage HK542, complete genome
Enterobacteria phage HK542, complete genome
gi|428783345|ref|NC_019769.1||gnl|N ENOMES|31825

Nucleotide
glycogen/starch/alpha-glucan phosphorylase [Lederbergia lenta]
glycogen/starch/alpha-glucan phosphorylase [Lederbergia lenta]
gi|1403634523|emb|SQI61229.1|

Protein

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
SCV000820115	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 10, 2024)	germline	clinical testing	PubMed (16) [See all records that cite these PMIDs] 7987387, 10390011, 10861313, 11556834, 12072543, 18363633, 22841127, 7566978, 7647780, 10389768, 10491434, 10498896, 19260062, 20340136, 21462282, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000820115

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 10, 2024)

germline

clinical testing

PubMed (16)
[See all records that cite these PMIDs]

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

Germline p16 mutations in familial melanoma.

Hussussian CJ, Struewing JP, Goldstein AM, Higgins PA, Ally DS, Sheahan MD, Clark WH Jr, Tucker MA, Dracopoli NC.

Nat Genet. 1994 Sep;8(1):15-21.

PubMed [citation]

PMID:: 7987387

Mutation testing in melanoma families: INK4A, CDK4 and INK4D.

Newton Bishop JA, Harland M, Bennett DC, Bataille V, Goldstein AM, Tucker MA, Ponder BA, Cuzick J, Selby P, Bishop DT.

Br J Cancer. 1999 Apr;80(1-2):295-300.

PubMed [citation]

PMID:: 10390011
PMCID:: PMC2363010

See all PubMed Citations (16)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000820115.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (16)

Description

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 71 of the CDKN2A (p16INK4a) protein (p.Asn71Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with melanoma (PMID: 7987387, 10390011, 10861313, 11556834, 12072543, 18363633, 21462282, 22841127). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Asn63Ser. ClinVar contains an entry for this variant (Variation ID: 418121). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. Experimental studies have shown that this missense change affects CDKN2A (p16INK4a) function (PMID: 7566978, 7647780, 10389768, 10491434, 10498896, 19260062, 20340136, 21462282). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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