rs1187336837

chr4-88007930-AC-Achr4-88007930-AC-ACC

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_000297.4(PKD2):c.203del(p.Pro68ArgfsTer49) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKD2 NM_000297.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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]

(HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 4-88007930-AC-A is Pathogenic according to our data. Variant chr4-88007930-AC-A is described in Lovd as [Pathogenic]. Variant chr4-88007930-AC-A is described in Lovd as [Pathogenic]. Variant chr4-88007930-AC-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2	NM_000297.4	c.203del	p.Pro68ArgfsTer49	frameshift_variant	1/15	ENST00000237596.7
PKD2	XM_011532028.3	c.203del	p.Pro68ArgfsTer49	frameshift_variant	1/14
PKD2	NR_156488.2	n.302del		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2	ENST00000237596.7	c.203del	p.Pro68ArgfsTer49	frameshift_variant	1/15	1	NM_000297.4	P1
	ENST00000662475.1	n.112+435del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150276 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000116 AC: 15 AN: 1295770 Hom.: 0 Cov.: 33 AF XY: 0.0000126 AC XY: 8 AN XY: 636876

Gnomad4 AFR exome AF: 0.0000376

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000442

Gnomad4 EAS exome AF: 0.0000352

Gnomad4 SAS exome AF: 0.0000282

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000875

Gnomad4 OTH exome AF: 0.0000188

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 150276 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73374

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1187336837; hg19: chr4-88929082;