rs17013754

Variant names:

• chr4-88046681-A-G
• rs17013754
• NM_000297.4:c.1359A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-88046681-A-G
• chr4-88046681-A-C
• chr4-88046681-A-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_000297.4(PKD2):​c.1359A>G​(p.Pro453Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,526 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (16 hom.)
• Consequence: PKD2 NM_000297.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.265
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• polycystic kidney disease 2

  Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 4-88046681-A-G is Benign according to our data. Variant chr4-88046681-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 92792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.265 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0092 (1401/152346) while in subpopulation AFR AF = 0.0316 (1312/41568). AF 95% confidence interval is 0.0301. There are 17 homozygotes in GnomAd4. There are 704 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000297.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	NM_000297.4	MANE Select	c.1359A>G	p.Pro453Pro	synonymous	Exon 6 of 15	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.1134A>G	p.Pro378Pro	synonymous	Exon 5 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.1458A>G		non_coding_transcript_exon	Exon 6 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.1359A>G	p.Pro453Pro	synonymous	Exon 6 of 15	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.1359A>G	p.Pro453Pro	synonymous	Exon 6 of 15	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.1359A>G	p.Pro453Pro	synonymous	Exon 6 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.00914 AC: 1392 AN: 152228 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00261 AC: 655 AN: 251404 AF XY: 0.00203

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00103 AC: 1500 AN: 1461180 Hom.: 16 Cov.: 30 AF XY: 0.000923 AC XY: 671 AN XY: 726950

African (AFR) AF: 0.0325 AC: 1089 AN: 33464

American (AMR) AF: 0.00172 AC: 77 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000823 AC: 71 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5758

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111406

Other (OTH) AF: 0.00287 AC: 173 AN: 60354

GnomAD4 genome AF: 0.00920 AC: 1401 AN: 152346 Hom.: 17 Cov.: 32 AF XY: 0.00945 AC XY: 704 AN XY: 74494

African (AFR) AF: 0.0316 AC: 1312 AN: 41568

American (AMR) AF: 0.00327 AC: 50 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68042

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00449 Hom.: 15

Bravo AF: 0.0106

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	Polycystic kidney disease 2 (3)
-	-	2	not specified (2)
-	-	1	Autosomal dominant polycystic kidney disease (1)
-	-	1	Polycystic kidney disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.4
DANN	Benign	0.72
PhyloP100		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs17013754; hg19: chr4-88967833; COSMIC: COSV99418196;