rs1554938197
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001122630.2(CDKN1C):c.156_157insTTCCAGCTGG(p.Asp53PhefsTer64) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y52Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
CDKN1C
NM_001122630.2 frameshift
NM_001122630.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.91
Genes affected
CDKN1C (HGNC:1786): (cyclin dependent kinase inhibitor 1C) This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-2885300-C-CCCAGCTGGAA is Pathogenic according to our data. Variant chr11-2885300-C-CCCAGCTGGAA is described in ClinVar as [Pathogenic]. Clinvar id is 524696.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKN1C | NM_001122630.2 | c.156_157insTTCCAGCTGG | p.Asp53PhefsTer64 | frameshift_variant | 2/4 | ENST00000440480.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKN1C | ENST00000440480.8 | c.156_157insTTCCAGCTGG | p.Asp53PhefsTer64 | frameshift_variant | 2/4 | 1 | NM_001122630.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Beckwith-Wiedemann syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 18, 2021 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CDKN1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 524696). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp64Phefs*64) in the CDKN1C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDKN1C are known to be pathogenic (PMID: 20503313). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at