rs1553924158
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000297.4(PKD2):c.603G>A(p.Trp201Ter) variant causes a stop gained change involving the alteration of a 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 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
PKD2
NM_000297.4 stop_gained
NM_000297.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 7.49
Genes affected
PKD2 (HGNC:9009): (polycystin 2, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein is a multi-pass membrane protein that functions as a calcium permeable cation channel, and is involved in calcium transport and calcium signaling in renal epithelial cells. This protein interacts with polycystin 1, and they may be partners in a common signaling cascade involved in tubular morphogenesis. Mutations in this gene are associated with autosomal dominant polycystic kidney disease type 2. [provided by RefSeq, Mar 2011]
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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 4-88019465-G-A is Pathogenic according to our data. Variant chr4-88019465-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 448038.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2 | NM_000297.4 | c.603G>A | p.Trp201Ter | stop_gained | 2/15 | ENST00000237596.7 | |
PKD2 | XM_011532028.3 | c.603G>A | p.Trp201Ter | stop_gained | 2/14 | ||
PKD2 | NR_156488.2 | n.702G>A | non_coding_transcript_exon_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2 | ENST00000237596.7 | c.603G>A | p.Trp201Ter | stop_gained | 2/15 | 1 | NM_000297.4 | P1 | |
PKD2 | ENST00000506727.1 | n.105G>A | non_coding_transcript_exon_variant | 2/4 | 4 |
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: 1393204Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 697314
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1393204
Hom.:
Cov.:
25
AF XY:
AC XY:
0
AN XY:
697314
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 03, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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