rs2728111

Positions:

• chr4-88030984-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000297.4(PKD2):​c.710-5236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,254 control chromosomes in the GnomAD database, including 49,967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (49967 hom., cov: 33)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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]

PKD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD2	NM_000297.4	c.710-5236C>T		intron_variant		ENST00000237596.7	NP_000288.1
PKD2	XM_011532028.3	c.710-5236C>T		intron_variant			XP_011530330.1
PKD2	XM_011532029.2	c.-67-101C>T		intron_variant			XP_011530331.1
PKD2	NR_156488.2	n.809-5236C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD2	ENST00000237596.7	c.710-5236C>T		intron_variant		1	NM_000297.4	ENSP00000237596.2
PKD2	ENST00000506727.1	n.212-5152C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122777 AN: 152136 Hom.: 49919 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.766

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.807 AC: 122881 AN: 152254 Hom.: 49967 Cov.: 33 AF XY: 0.810 AC XY: 60331 AN XY: 74450

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.766

Alfa AF: 0.787 Hom.: 14474

Bravo AF: 0.807

Asia WGS AF: 0.778 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.72

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: rs2728111; hg19: chr4-88952136;