2-42048424-C-CG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_138370.3(PKDCC):c.228dup(p.Pro77AlafsTer95) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 973,354 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000010 ( 0 hom. )
Consequence
PKDCC
NM_138370.3 frameshift
NM_138370.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.263
Genes affected
PKDCC (HGNC:25123): (protein kinase domain containing, cytoplasmic) Enables non-membrane spanning protein tyrosine kinase activity. Involved in peptidyl-tyrosine phosphorylation and skeletal system development. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
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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 2-42048424-C-CG is Pathogenic according to our data. Variant chr2-42048424-C-CG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1803946.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKDCC | NM_138370.3 | c.228dup | p.Pro77AlafsTer95 | frameshift_variant | 1/7 | ENST00000294964.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKDCC | ENST00000294964.6 | c.228dup | p.Pro77AlafsTer95 | frameshift_variant | 1/7 | 1 | NM_138370.3 | P1 | |
PKDCC | ENST00000401498.6 | c.198+30dup | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome AF: 0.00000103 AC: 1AN: 973354Hom.: 0 Cov.: 30 AF XY: 0.00000215 AC XY: 1AN XY: 464314
GnomAD4 exome
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1
AN:
973354
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30
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1
AN XY:
464314
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GnomAD4 genome ? Cov.: 30
GnomAD4 genome
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Cov.:
30
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rhizomelic limb shortening with dysmorphic features Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genomic Medicine Theme, NIHR Oxford Biomedical Research Centre, University of Oxford | Nov 28, 2022 | Sajan et al. (2019) reported 2 unrelated patients with rhizomelic limb shortening, variable dysmorphic features and biallelic predicted loss of function variants in PKDCC. Short limbs were previously described in a mouse model (Imuta et al, 2009). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.