4-88038770-G-C

Position:

• chr4-88038770-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000297.4(PKD2):​c.1094+269G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,976 control chromosomes in the GnomAD database, including 23,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (23788 hom., cov: 32)
• Consequence: PKD2 NM_000297.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.321

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-88038770-G-C is Benign according to our data. Variant chr4-88038770-G-C is described in ClinVar as [Benign]. Clinvar id is 1234483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2	NM_000297.4	c.1094+269G>C		intron_variant		ENST00000237596.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2	ENST00000237596.7	c.1094+269G>C		intron_variant		1	NM_000297.4	P1
PKD2	ENST00000506367.1	n.541+269G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82314 AN: 151858 Hom.: 23729 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.542 AC: 82440 AN: 151976 Hom.: 23788 Cov.: 32 AF XY: 0.536 AC XY: 39802 AN XY: 74276

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.501

Alfa AF: 0.460 Hom.: 8316

Bravo AF: 0.551

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.35

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: rs2725220; hg19: chr4-88959922;