chr16-2093886-CG-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 9P and 1B. PVS1PP5BS2_Supporting
The NM_001009944.3(PKD1):c.10745del(p.Pro3582ArgfsTer3) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000444 in 1,576,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
PKD1
NM_001009944.3 frameshift
NM_001009944.3 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.53
Genes affected
PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 16-2093886-CG-C is Pathogenic according to our data. Variant chr16-2093886-CG-C is described in Lovd as [Pathogenic]. Variant chr16-2093886-CG-C is described in Lovd as [Pathogenic].
BS2
High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.10745del | p.Pro3582ArgfsTer3 | frameshift_variant | 36/46 | ENST00000262304.9 | |
PKD1-AS1 | NR_135175.1 | n.304-829del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.10745del | p.Pro3582ArgfsTer3 | frameshift_variant | 36/46 | 1 | NM_001009944.3 | P5 | |
PKD1-AS1 | ENST00000563284.3 | n.195-829del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000421 AC: 6AN: 1424610Hom.: 0 Cov.: 33 AF XY: 0.00000424 AC XY: 3AN XY: 706968
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74298
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at