16-2102387-C-G

Variant names:

• chr16-2102387-C-G
• rs9935834
• NM_001009944.3:c.9195G>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_001009944.3(PKD1):​c.9195G>C​(p.Val3065Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,555,570 control chromosomes in the GnomAD database, including 27,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6325 hom., cov: 33)
  • Exomes 𝑓: 0.16 (21588 hom.)
• Consequence: PKD1 NM_001009944.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.786
• Publications: 10 publications found

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

PKD1 Gene-Disease associations (from GenCC):

• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• polycystic kidney disease 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive polycystic kidney disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Caroli disease

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-2102387-C-G is Benign according to our data. Variant chr16-2102387-C-G is described in ClinVar as Benign. ClinVar VariationId is 257039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.786 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.9195G>C	p.Val3065Val	synonymous	Exon 25 of 46	NP_001009944.3
	PKD1	NM_000296.4		c.9195G>C	p.Val3065Val	synonymous	Exon 25 of 46	NP_000287.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.9195G>C	p.Val3065Val	synonymous	Exon 25 of 46	ENSP00000262304.4
	PKD1	ENST00000423118.5	TSL:1	c.9195G>C	p.Val3065Val	synonymous	Exon 25 of 46	ENSP00000399501.1
	PKD1	ENST00000480227.5	TSL:1	n.932G>C		non_coding_transcript_exon	Exon 3 of 8

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37356 AN: 151642 Hom.: 6306 Cov.: 33

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.156 AC: 24792 AN: 158570 AF XY: 0.149

Gnomad AFR exome AF: 0.504

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.000260

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.164 AC: 229811 AN: 1403812 Hom.: 21588 Cov.: 35 AF XY: 0.160 AC XY: 111141 AN XY: 693440

African (AFR) AF: 0.495 AC: 15758 AN: 31834

American (AMR) AF: 0.127 AC: 4616 AN: 36252

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 5952 AN: 25216

East Asian (EAS) AF: 0.000436 AC: 16 AN: 36690

South Asian (SAS) AF: 0.0747 AC: 6005 AN: 80398

European-Finnish (FIN) AF: 0.181 AC: 8788 AN: 48570

Middle Eastern (MID) AF: 0.229 AC: 934 AN: 4070

European-Non Finnish (NFE) AF: 0.164 AC: 177459 AN: 1082572

Other (OTH) AF: 0.177 AC: 10283 AN: 58210

GnomAD4 genome AF: 0.247 AC: 37419 AN: 151758 Hom.: 6325 Cov.: 33 AF XY: 0.241 AC XY: 17871 AN XY: 74226

African (AFR) AF: 0.482 AC: 19824 AN: 41156

American (AMR) AF: 0.184 AC: 2804 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.0698 AC: 337 AN: 4830

European-Finnish (FIN) AF: 0.188 AC: 1988 AN: 10588

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11008 AN: 67952

Other (OTH) AF: 0.230 AC: 483 AN: 2104

Alfa AF: 0.156 Hom.: 719

Bravo AF: 0.259

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 27, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 25, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15772804, 10854095, 18837007, 22608885, 24374109)

Polycystic kidney disease, adult type Benign:1

May 08, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal dominant polycystic kidney disease Benign:1

Jan 01, 2019

Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.55
DANN	Benign	0.60
PhyloP100		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs9935834; hg19: chr16-2152388; COSMIC: COSV51923518; COSMIC: COSV51923518;