rs2728118

Variant names:

• chr4-88008153-G-A
• rs2728118
• NM_000297.4:c.420G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-88008153-G-A
• chr4-88008153-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000297.4(PKD2):​c.420G>A​(p.Gly140Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,462,896 control chromosomes in the GnomAD database, including 9,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (929 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8372 hom.)
• Consequence: PKD2 NM_000297.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.02
• Publications: 19 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

ENSG00000286618 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 4-88008153-G-A is Benign according to our data. Variant chr4-88008153-G-A is described in ClinVar as Benign. ClinVar VariationId is 92795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

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.420G>A	p.Gly140Gly	synonymous	Exon 1 of 15	NP_000288.1	Q13563-1
	PKD2	NM_001440544.1		c.420G>A	p.Gly140Gly	synonymous	Exon 1 of 14	NP_001427473.1
	PKD2	NR_156488.2		n.519G>A		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD2	ENST00000237596.7	TSL:1 MANE Select	c.420G>A	p.Gly140Gly	synonymous	Exon 1 of 15	ENSP00000237596.2	Q13563-1
	PKD2	ENST00000927447.1		c.420G>A	p.Gly140Gly	synonymous	Exon 1 of 15	ENSP00000597506.1
	PKD2	ENST00000927448.1		c.420G>A	p.Gly140Gly	synonymous	Exon 1 of 14	ENSP00000597507.1

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13486 AN: 151746 Hom.: 924 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0981

Gnomad OTH AF: 0.0795

GnomAD2 exomes AF: 0.133 AC: 11224 AN: 84630 AF XY: 0.118

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.0654

Gnomad EAS exome AF: 0.290

Gnomad FIN exome AF: 0.0763

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.104 AC: 135815 AN: 1311042 Hom.: 8372 Cov.: 36 AF XY: 0.102 AC XY: 65698 AN XY: 646084

African (AFR) AF: 0.0246 AC: 657 AN: 26690

American (AMR) AF: 0.257 AC: 7207 AN: 28094

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 1525 AN: 22826

East Asian (EAS) AF: 0.306 AC: 8820 AN: 28852

South Asian (SAS) AF: 0.0613 AC: 4376 AN: 71426

European-Finnish (FIN) AF: 0.0753 AC: 2444 AN: 32444

Middle Eastern (MID) AF: 0.0621 AC: 269 AN: 4332

European-Non Finnish (NFE) AF: 0.101 AC: 104739 AN: 1042170

Other (OTH) AF: 0.107 AC: 5778 AN: 54208

GnomAD4 genome AF: 0.0890 AC: 13515 AN: 151854 Hom.: 929 Cov.: 32 AF XY: 0.0906 AC XY: 6721 AN XY: 74224

African (AFR) AF: 0.0279 AC: 1157 AN: 41510

American (AMR) AF: 0.187 AC: 2861 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0652 AC: 226 AN: 3468

East Asian (EAS) AF: 0.259 AC: 1321 AN: 5108

South Asian (SAS) AF: 0.0594 AC: 287 AN: 4828

European-Finnish (FIN) AF: 0.0735 AC: 771 AN: 10488

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0981 AC: 6659 AN: 67872

Other (OTH) AF: 0.0834 AC: 176 AN: 2110

Alfa AF: 0.0890 Hom.: 141

Bravo AF: 0.0953

Asia WGS AF: 0.153 AC: 525 AN: 3456

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Autosomal dominant polycystic kidney disease (2)
-	-	2	Polycystic kidney disease 2 (2)
-	-	1	not specified (1)
-	-	1	PKD2-related disorder (1)
-	-	1	Polycystic kidney disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.6
DANN	Uncertain	0.98
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

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: rs2728118; hg19: chr4-88929305; COSMIC: COSV52940231; COSMIC: COSV52940231;