NM_000077.5(CDKN2A):c.106G>A (p.Ala36Thr) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 14, 2020
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:: RCV001174614.1

Allele description [Variation Report for NM_000077.5(CDKN2A):c.106G>A (p.Ala36Thr)]

NM_000077.5(CDKN2A):c.106G>A (p.Ala36Thr)

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.106G>A (p.Ala36Thr)

HGVS:

NC_000009.12:g.21974722C>T
NG_007485.1:g.24770G>A
NM_000077.5:c.106G>AMANE SELECT
NM_001195132.2:c.106G>A
NM_001363763.2:c.-3-3514G>A
NM_058195.4:c.194-3514G>A
NM_058197.5:c.106G>A
NP_000068.1:p.Ala36Thr
NP_000068.1:p.Ala36Thr
NP_001182061.1:p.Ala36Thr
NP_478104.2:p.Ala36Thr
LRG_11t1:c.106G>A
LRG_11:g.24770G>A
LRG_11p1:p.Ala36Thr
NC_000009.11:g.21974721C>T
NM_000077.3:c.106G>A
NM_000077.4:c.106G>A

Protein change:

A36T

Links:

dbSNP: rs777948908

NCBI 1000 Genomes Browser:

rs777948908

Molecular consequence:

NM_001363763.2:c.-3-3514G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_058195.4:c.194-3514G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000077.5:c.106G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001195132.2:c.106G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_058197.5:c.106G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001337816	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 14, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 31382929, 17055252, 14722037, 30274933 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001337816

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 14, 2020)

germline

clinical testing

PubMed (4)
[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

Germline and somatic mutations in patients with multiple primary melanomas: a next generation sequencing study.

Casula M, Paliogiannis P, Ayala F, De Giorgi V, Stanganelli I, Mandalà M, Colombino M, Manca A, Sini MC, Caracò C, Ascierto PA, Satta RR; Melanoma Unit of Sassari (MUS)., Lissia A, Cossu A, Palmieri G; Italian Melanoma Intergroup (IMI)..

BMC Cancer. 2019 Aug 5;19(1):772. doi: 10.1186/s12885-019-5984-7.

PubMed [citation]

PMID:: 31382929
PMCID:: PMC6683413

Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy.

Casula M, Colombino M, Satta MP, Cossu A, Lissia A, Budroni M, Simeone E, Calemma R, Loddo C, Caracò C, Mozzillo N, Daponte A, Comella G, Canzanella S, Guida M, Castello G, Ascierto PA, Palmieri G; Italian Melanoma Intergroup..

Eur J Cancer. 2007 Jan;43(1):137-43. Epub 2006 Oct 19.

PubMed [citation]

PMID:: 17055252

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001337816.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: CDKN2A c.106G>A (p.Ala36Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 244176 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.106G>A has been reported in the literature in individuals affected with melanoma (Casula_2004, Casula_2007, Dalmasso_2019, Casula_2019). These reports do not provide unequivocal conclusions about association of the variant with Cutaneous Malignant Melanoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Jun 17, 2024

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