This sequence change affects a donor splice site in intron 1 of the CDKN2A (p16INK4a) gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CDKN2A (p16INK4a) are known to be pathogenic (PMID: 15146471, 16905682). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Likely pathogenic
- Review status:
- criteria provided, single submitter
- Submissions:
- 1
- First in ClinVar:
- Apr 17, 2017
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Sep 16, 2021
- Accession:
- VCV000406712.5
- Variation ID:
- 406712
- Description:
- single nucleotide variant
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NM_000077.5(CDKN2A):c.150+2T>C
- Allele ID
- 397437
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 9p21.3
- Genomic location
- 9: 21974676 (GRCh38) GRCh38 UCSC
- 9: 21974675 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000077.5:c.150+2T>C MANE Select splice donor NM_058195.4:c.194-3468T>C MANE Plus Clinical NM_001195132.2:c.150+2T>C splice donor NM_001363763.2:c.-3-3468T>C NM_058197.5:c.152T>C NP_478104.2:p.Val51Ala missense NC_000009.12:g.21974676A>G NC_000009.11:g.21974675A>G NG_007485.1:g.24816T>C LRG_11:g.24816T>C LRG_11t1:c.150+2T>C - Protein change
- V51A
- Other names
- -
- Canonical SPDI
- NC_000009.12:21974675:A:G
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- ClinGen: CA16612864
- dbSNP: rs1060501265
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Likely pathogenic | 1 | criteria provided, single submitter | Sep 16, 2021 | RCV000459258.5 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| CDKN2A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1169 | 1268 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Likely pathogenic
(Sep 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial melanoma
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000545534.4
First in ClinVar: Apr 17, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change affects a donor splice site in intron 1 of the CDKN2A (p16INK4a) gene. It is expected to disrupt RNA splicing. Variants that … (more)
This sequence change affects a donor splice site in intron 1 of the CDKN2A (p16INK4a) gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CDKN2A (p16INK4a) are known to be pathogenic (PMID: 15146471, 16905682). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CDKN2A (p16INK4a)-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. (less)
|
Functional evidence
Help| 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 this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. | Goldstein AM | Journal of medical genetics | 2007 | PMID: 16905682 |
| Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
| Familial melanoma, pancreatic cancer and germline CDKN2A mutations. | Goldstein AM | Human mutation | 2004 | PMID: 15146471 |
Text-mined citations for rs1060501265...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Feb 07, 2023