rs1553924173

Positions:

• chr4-88019531-AC-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000297.4(PKD2):​c.670del​(p.Leu224TrpfsTer9) 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 (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PKD2 NM_000297.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.0710

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]

ACMG classification

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 4-88019531-AC-A is Pathogenic according to our data. Variant chr4-88019531-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 434013.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.670del	p.Leu224TrpfsTer9	frameshift_variant	2/15	ENST00000237596.7
PKD2	XM_011532028.3	c.670del	p.Leu224TrpfsTer9	frameshift_variant	2/14
PKD2	NR_156488.2	n.769del		non_coding_transcript_exon_variant	2/14
PKD2	XM_011532029.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2	ENST00000237596.7	c.670del	p.Leu224TrpfsTer9	frameshift_variant	2/15	1	NM_000297.4	P1
PKD2	ENST00000506727.1	n.172del		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive polycystic kidney disease Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

Aug 25, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553924173; hg19: chr4-88940683;