16-2110502-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001009944.3(PKD1):c.4665A>C(p.Ala1555Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,016 control chromosomes in the GnomAD database, including 30,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1555A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.25 ( 6671 hom., cov: 34)

Exomes 𝑓: 0.17 ( 23692 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.74

Publications

22 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 16-2110502-T-G is Benign according to our data. Variant chr16-2110502-T-G is described in ClinVar as Benign. ClinVar VariationId is 256968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 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.4665A>C	p.Ala1555Ala	synonymous	Exon 15 of 46	NP_001009944.3
	PKD1	NM_000296.4		c.4665A>C	p.Ala1555Ala	synonymous	Exon 15 of 46	NP_000287.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PKD1	ENST00000262304.9	TSL:1 MANE Select	c.4665A>C	p.Ala1555Ala	synonymous	Exon 15 of 46	ENSP00000262304.4
PKD1	ENST00000423118.5	TSL:1	c.4665A>C	p.Ala1555Ala	synonymous	Exon 15 of 46	ENSP00000399501.1
PKD1	ENST00000488185.2	TSL:5	c.471-2144A>C		intron	N/A	ENSP00000456672.1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38340

AN:

152084

Hom.:

6649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0882

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.246

GnomAD2 exomes

AF:

0.164

AC:

40642

AN:

248566

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.168

AC:

244989

AN:

1459814

Hom.:

23692

Cov.:

AF XY:

0.165

AC XY:

119809

AN XY:

726224

show subpopulations

African (AFR)

AF:

0.503

AC:

16824

AN:

33454

American (AMR)

AF:

0.121

AC:

5397

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6237

AN:

26118

East Asian (EAS)

AF:

0.000277

AC:

AN:

39698

South Asian (SAS)

AF:

0.0900

AC:

7763

AN:

86232

European-Finnish (FIN)

AF:

0.183

AC:

9517

AN:

51874

Middle Eastern (MID)

AF:

0.236

AC:

1329

AN:

5622

European-Non Finnish (NFE)

AF:

0.168

AC:

187024

AN:

1111770

Other (OTH)

AF:

0.180

AC:

10887

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

13965

27929

41894

55858

69823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6720

13440

20160

26880

33600

<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:

0.252

AC:

38409

AN:

152202

Hom.:

6671

Cov.:

AF XY:

0.248

AC XY:

18421

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.489

AC:

20294

AN:

41508

American (AMR)

AF:

0.185

AC:

2835

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

817

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5190

South Asian (SAS)

AF:

0.0878

AC:

424

AN:

4828

European-Finnish (FIN)

AF:

0.191

AC:

2032

AN:

10612

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11293

AN:

67980

Other (OTH)

AF:

0.244

AC:

515

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1360

2720

4080

5440

6800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.154

Hom.:

696

Bravo

AF:

0.264

Asia WGS

AF:

0.0770

AC:

269

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.177

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

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

not provided

Benign:2

Dec 19, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22008521)

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Polycystic kidney disease, adult type

Benign:1

Jul 07, 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

The c.4665A>C, p.Ala1555Ala variant was identified in 16.87% of 20079 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015).

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

-0.57

CADD

Benign

3.8

(source)

DANN

Benign

0.67

PhyloP100

1.7

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over