rs761532715
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_138370.3(PKDCC):c.651C>A(p.Tyr217Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PKDCC
NM_138370.3 stop_gained
NM_138370.3 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 1.23
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 2-42053250-C-A is Pathogenic according to our data. Variant chr2-42053250-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521769.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.651C>A | p.Tyr217Ter | stop_gained | 2/7 | ENST00000294964.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKDCC | ENST00000294964.6 | c.651C>A | p.Tyr217Ter | stop_gained | 2/7 | 1 | NM_138370.3 | P1 | |
PKDCC | ENST00000485578.1 | n.272C>A | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
PKDCC | ENST00000492861.1 | n.77C>A | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
PKDCC | ENST00000401498.6 | c.509C>A | p.Thr170Asn | missense_variant, NMD_transcript_variant | 3/8 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1418560Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 705750
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1418560
Hom.:
Cov.:
36
AF XY:
AC XY:
0
AN XY:
705750
Gnomad4 AFR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ExAC
?
AF:
AC:
8
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 17, 2017 | - - |
Rhizomelic limb shortening with dysmorphic features Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 20, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at