rs2725222

chr4-88037340-G-Achr4-88037340-G-T

Variant summary

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

The NM_000297.4(PKD2):c.844-911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,048 control chromosomes in the GnomAD database, including 14,213 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 0.43 (14213 hom., cov: 32)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2	NM_000297.4	c.844-911G>A		intron_variant		ENST00000237596.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2	ENST00000237596.7	c.844-911G>A		intron_variant		1	NM_000297.4	P1
PKD2	ENST00000506367.1	n.291-911G>A		intron_variant, non_coding_transcript_variant		3
PKD2	ENST00000506727.1	n.430-911G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65541 AN: 151928 Hom.: 14188 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.432 AC: 65634 AN: 152048 Hom.: 14213 Cov.: 32 AF XY: 0.428 AC XY: 31823 AN XY: 74320

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.411

Alfa AF: 0.411 Hom.: 7493

Bravo AF: 0.431

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.20
Dann	Benign	0.38

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: rs2725222; hg19: chr4-88958492;