chr16-2100322-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.9569-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 1,575,576 control chromosomes in the GnomAD database, including 9,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3570 hom., cov: 33)

Exomes 𝑓: 0.064 ( 5812 hom. )

Consequence

PKD1
NM_001009944.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.04

Publications

8 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 (BayesDel_noAF=-0.92).

BP6

Variant 16-2100322-A-G is Benign according to our data. Variant chr16-2100322-A-G is described in ClinVar as Benign. ClinVar VariationId is 257043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.9569-13T>C		intron_variant	Intron 27 of 45	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.9569-13T>C		intron_variant	Intron 27 of 45	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24303

AN:

152130

Hom.:

3550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0950

Gnomad ASJ

AF:

0.0882

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0470

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0679

Gnomad OTH

AF:

0.140

GnomAD2 exomes

AF:

0.0388

AC:

8895

AN:

229308

AF XY:

0.0336

show subpopulations

Gnomad AFR exome

AF:

0.284

Gnomad AMR exome

AF:

0.0277

Gnomad ASJ exome

AF:

0.0354

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0564

Gnomad NFE exome

AF:

0.0245

Gnomad OTH exome

AF:

0.0345

GnomAD4 exome

AF:

0.0642

AC:

91385

AN:

1423328

Hom.:

5812

Cov.:

AF XY:

0.0631

AC XY:

44740

AN XY:

709398

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.379

AC:

11459

AN:

30274

American (AMR)

AF:

0.0499

AC:

2208

AN:

44258

Ashkenazi Jewish (ASJ)

AF:

0.0912

AC:

2341

AN:

25670

East Asian (EAS)

AF:

0.000353

AC:

AN:

39692

South Asian (SAS)

AF:

0.0422

AC:

3610

AN:

85494

European-Finnish (FIN)

AF:

0.111

AC:

5767

AN:

52186

Middle Eastern (MID)

AF:

0.0696

AC:

282

AN:

4052

European-Non Finnish (NFE)

AF:

0.0565

AC:

61137

AN:

1082756

Other (OTH)

AF:

0.0775

AC:

4567

AN:

58946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.363

Heterozygous variant carriers

3728

7456

11183

14911

18639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2190

4380

6570

8760

10950

<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:

0.160

AC:

24363

AN:

152248

Hom.:

3570

Cov.:

AF XY:

0.159

AC XY:

11810

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.390

AC:

16210

AN:

41536

American (AMR)

AF:

0.0949

AC:

1452

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0882

AC:

306

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5172

South Asian (SAS)

AF:

0.0464

AC:

224

AN:

4826

European-Finnish (FIN)

AF:

0.115

AC:

1224

AN:

10614

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0679

AC:

4615

AN:

68004

Other (OTH)

AF:

0.138

AC:

292

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

908

1816

2723

3631

4539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.0587

Hom.:

106

Bravo

AF:

0.167

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 25, 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

Dec 30, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22008521, 17574468, 11967008) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Polycystic kidney disease, adult type

Benign:1

Jun 02, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic kidney disease

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PKD1, c.9569-13T>C, (Alias: IVS27-13T>C), Heterozygous, Benign The PKD1 c.9569-13T>C variant was identified in 22 of 328 proband chromosomes (frequency: 0.067) from individuals or families with ADPKD or renal disease, and was not identified in 100 control chromosomes from healthy individuals (Bataille 2011, Garcia-Gonzalez 2007, Rossetti 2002). All the above studies have identified the variant as a polymorphism. The c.9569-13T>C variant was identified in the dbSNP (ID: rs11248911) with unknown clinical significance with a minor allele frequency 0.1556 (779 of 5000 chromosomes in 1000 Genome Project). The variant was not identified In the NHLBI Exome Sequencing Project (Exome Variant Server). The variant was identified in Exome Aggregation Consortium (March 14, 2016) in 5596 of 114186 chromosomes (frequency: 0.04901) or 330 of 6146 of European (Finnish), 2393 of 62978 European (Non-Finnish), 2033 of 8090 African, 193 of 11226 Latino, 601 of 16298 South Asians, 3 of 8592 East Asians and 43 of 856 Other populations. The variant was identified in PKD Mutation Database and classified as likely neutral and not predicted to alter splicing. The c.9569-13T>C variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign. -

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

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.045

(source)

DANN

Benign

0.28

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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