ClinVar Genomic variation as it relates to human health
NM_000077.5(CDKN2A):c.318G>A (p.Val106=)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(5); Benign(2); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000077.5(CDKN2A):c.318G>A (p.Val106=)
Variation ID: 135826 Accession: VCV000135826.53
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p21.3 9: 21971041 (GRCh38) [ NCBI UCSC ] 9: 21971040 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 29, 2016 May 12, 2024 Feb 6, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000077.5:c.318G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000068.1:p.Val106= synonymous NM_058195.4:c.361G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_478102.2:p.Ala121Thr missense NM_001195132.2:c.318G>A NP_001182061.1:p.Val106= synonymous NM_001363763.2:c.165G>A NP_001350692.1:p.Val55= synonymous NM_058197.5:c.*241G>A 3 prime UTR NC_000009.12:g.21971041C>T NC_000009.11:g.21971040C>T NG_007485.1:g.28451G>A LRG_11:g.28451G>A LRG_11t1:c.318G>A LRG_11p1:p.Val106= LRG_11t2:c.361G>A LRG_11p2:p.Ala121Thr - Protein change
- A121T
- Other names
- p.A121T:GCG>ACG
- Canonical SPDI
- NC_000009.12:21971040:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00011
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
The Genome Aggregation Database (gnomAD), exomes 0.00022
The Genome Aggregation Database (gnomAD) 0.00026
Trans-Omics for Precision Medicine (TOPMed) 0.00026
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CDKN2A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1236 | 1387 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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May 19, 2016 | RCV000160416.9 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Feb 6, 2024 | RCV000212401.15 | |
Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
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Oct 30, 2023 | RCV000590444.36 | |
Benign (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000988150.3 | |
Likely benign (1) |
criteria provided, single submitter
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Nov 1, 2022 | RCV001050185.9 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV002467577.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Nov 20, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000805824.2
First in ClinVar: Mar 17, 2018 Last updated: Dec 23, 2019 |
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Uncertain significance
(-)
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criteria provided, single submitter
Method: research
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Maffucci syndrome
Affected status: yes
Allele origin:
maternal
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Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine
Accession: SCV002764253.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Benign
(Jun 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888053.3
First in ClinVar: Mar 17, 2018 Last updated: Dec 31, 2022 |
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Likely benign
(Nov 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Familial melanoma
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001214281.5
First in ClinVar: Apr 15, 2020 Last updated: Apr 09, 2023 |
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Uncertain significance
(Oct 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000210949.19
First in ClinVar: Feb 24, 2015 Last updated: Nov 25, 2023 |
Comment:
Observed in several individuals with melanoma, pancreatic cancer, or other cancers (PMID: 16234564, 17255954, 17218939, 21150883, 25787093, 26225579, 25479140, 26104880, 25980754, 26681309, 28726808, 34326862); In … (more)
Observed in several individuals with melanoma, pancreatic cancer, or other cancers (PMID: 16234564, 17255954, 17218939, 21150883, 25787093, 26225579, 25479140, 26104880, 25980754, 26681309, 28726808, 34326862); In silico analysis supports a deleterious effect on protein structure/function; Reported using an alternate transcript of the gene; Also known as p.Ala162Thr; This variant is associated with the following publications: (PMID: 25064638, 25980754, 30709382, 30039340, 16234564, 21150883, 26104880, 17218939, 12538475, 25787093, 26225579, 17255954, 28726808, 29415044, 27621404, 26681309, 19690981, 25780468, 27882345, 25479140, 16896043, 29641532, 11687599, 8710906, 16818274, 12532425, 27756164, 37322831, 28765326, 34326862, 27960642) (less)
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Uncertain significance
(Feb 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550353.5
First in ClinVar: Jul 27, 2022 Last updated: Feb 14, 2024 |
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Likely benign
(May 19, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000902687.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Melanoma-pancreatic cancer syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137762.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Uncertain significance
(Jun 10, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000214026.4
First in ClinVar: Mar 24, 2015 Last updated: May 29, 2016 |
Comment:
Insufficient or inconclusive evidence
Number of individuals with the variant: 1
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Likely benign
(Sep 04, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695342.3
First in ClinVar: Mar 17, 2018 Last updated: Oct 07, 2020 |
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Likely benign
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002498020.13
First in ClinVar: Apr 08, 2022 Last updated: May 12, 2024 |
Comment:
CDKN2A: BP4
Number of individuals with the variant: 3
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001966469.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002037434.1 First in ClinVar: Dec 21, 2021 Last updated: Dec 21, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807708.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742045.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history. | Chaffee KG | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 28726808 |
Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature. | Craddock CF | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28765326 |
Biallelic loss of CDKN2A is associated with poor response to treatment in pediatric acute lymphoblastic leukemia. | Braun M | Leukemia & lymphoma | 2017 | PMID: 27756164 |
The role of CDKN2A/B deletions in pediatric acute lymphoblastic leukemia. | Carrasco Salas P | Pediatric hematology and oncology | 2016 | PMID: 27960642 |
Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing. | Balmaña J | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2016 | PMID: 27621404 |
Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma. | Puig S | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681309 |
Novel CDKN2A mutations in Austrian melanoma patients. | Burgstaller-Muehlbacher S | Melanoma research | 2015 | PMID: 26225579 |
Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children. | Xu H | Nature communications | 2015 | PMID: 26104880 |
Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. | Yurgelun MB | Gastroenterology | 2015 | PMID: 25980754 |
Prevalence of Germline BAP1, CDKN2A, and CDK4 Mutations in an Australian Population-Based Sample of Cutaneous Melanoma Cases. | Aoude LG | Twin research and human genetics : the official journal of the International Society for Twin Studies | 2015 | PMID: 25787093 |
Prevalence and predictors of germline CDKN2A mutations for melanoma cases from Australia, Spain and the United Kingdom. | Harland M | Hereditary cancer in clinical practice | 2014 | PMID: 25780468 |
Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. | McWilliams RR | European journal of human genetics : EJHG | 2011 | PMID: 21150883 |
Mutational analysis of CDKN2A gene in a group of 390 larynx cancer patients. | Kiwerska K | Molecular biology reports | 2010 | PMID: 19690981 |
Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL. | Mullighan CG | Genes & development | 2008 | PMID: 18519632 |
Novel CDKN2A mutations detected in western Swedish families with hereditary malignant melanoma. | Erlandson A | The Journal of investigative dermatology | 2007 | PMID: 17255954 |
CDKN2A germline mutations in individuals with cutaneous malignant melanoma. | Orlow I | The Journal of investigative dermatology | 2007 | PMID: 17218939 |
The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma: an international population-based study. | Berwick M | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2006 | PMID: 16896043 |
The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951. | Mirebeau D | Haematologica | 2006 | PMID: 16818274 |
Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample. | Begg CB | Journal of the National Cancer Institute | 2005 | PMID: 16234564 |
Detecting homozygous deletions in the CDKN2A(p16(INK4a))/ARF(p14(ARF)) gene in urinary bladder cancer using real-time quantitative PCR. | Berggren P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2003 | PMID: 12538475 |
Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene. | Sakano S | International journal of cancer | 2003 | PMID: 12532425 |
Validation of denaturing high performance liquid chromatography as a rapid detection method for the identification of human INK4A gene mutations. | Orlow I | The Journal of molecular diagnostics : JMD | 2001 | PMID: 11687599 |
Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds. | Flores JF | Oncogene | 1997 | PMID: 9416844 |
Homozygous deletion of the p16/MTS1 gene in pediatric acute lymphoblastic leukemia is associated with unfavorable clinical outcome. | Kees UR | Blood | 1997 | PMID: 9166859 |
Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: analysis of a clinic-based population. | FitzGerald MG | Proceedings of the National Academy of Sciences of the United States of America | 1996 | PMID: 8710906 |
Homozygous deletions of the p16 tumor-suppressor gene are associated with lymphoid transformation of chronic myeloid leukemia. | Sill H | Blood | 1995 | PMID: 7718873 |
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Text-mined citations for rs199888003 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.