chr16-2102386-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001009944.3(PKD1):c.9196T>C(p.Phe3066Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,555,320 control chromosomes in the GnomAD database, including 27,908 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 6324 hom., cov: 33)

Exomes 𝑓: 0.16 ( 21584 hom. )

Consequence

PKD1
NM_001009944.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.610

Publications

12 publications found

Variant links:

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

PKD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.9981813E-4).

BP6

Variant 16-2102386-A-G is Benign according to our data. Variant chr16-2102386-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.9196T>C	p.Phe3066Leu	missense_variant	Exon 25 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.9196T>C	p.Phe3066Leu	missense_variant	Exon 25 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37355

AN:

151628

Hom.:

6305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0702

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:

24737

AN:

158300

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.503

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:

229760

AN:

1403576

Hom.:

21584

Cov.:

AF XY:

0.160

AC XY:

111113

AN XY:

693318

show subpopulations

African (AFR)

AF:

0.495

AC:

15755

AN:

31826

American (AMR)

AF:

0.127

AC:

4617

AN:

36238

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

5953

AN:

25218

East Asian (EAS)

AF:

0.000436

AC:

AN:

36684

South Asian (SAS)

AF:

0.0747

AC:

6000

AN:

80368

European-Finnish (FIN)

AF:

0.181

AC:

8789

AN:

48564

Middle Eastern (MID)

AF:

0.229

AC:

933

AN:

4068

European-Non Finnish (NFE)

AF:

0.164

AC:

177416

AN:

1082414

Other (OTH)

AF:

0.177

AC:

10281

AN:

58196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

11142

22284

33425

44567

55709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6492

12984

19476

25968

32460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.247

AC:

37418

AN:

151744

Hom.:

6324

Cov.:

AF XY:

0.241

AC XY:

17870

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.482

AC:

19828

AN:

41168

American (AMR)

AF:

0.184

AC:

2803

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

803

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5176

South Asian (SAS)

AF:

0.0697

AC:

336

AN:

4824

European-Finnish (FIN)

AF:

0.188

AC:

1986

AN:

10578

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11007

AN:

67946

Other (OTH)

AF:

0.229

AC:

483

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1140

2281

3421

4562

5702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.156

Hom.:

720

Bravo

AF:

0.259

ESP6500AA

AF:

0.315

AC:

1321

ESP6500EA

AF:

0.0838

AC:

698

ExAC

AF:

0.121

AC:

12389

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 04, 2025

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

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

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: 10854095) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.2

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.00070

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

0.61

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.085

Sift

Benign

0.66

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.21

B;P

Vest4

0.14

MutPred

0.44

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

ClinPred

0.0099

GERP RS

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.43

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over