chr16-2112978-G-A

Variant names:

• chr16-2112978-G-A
• rs2855349
• NM_001009944.3:c.2986-15C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001009944.3(PKD1):​c.2986-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,595,606 control chromosomes in the GnomAD database, including 2,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (249 hom., cov: 32)
  • Exomes 𝑓: 0.030 (2505 hom.)
• Consequence: PKD1 NM_001009944.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.570
• 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

ENSG00000261240 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-2112978-G-A is Benign according to our data. Variant chr16-2112978-G-A is described in ClinVar as [Benign]. Clinvar id is 256939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3	c.2986-15C>T		intron_variant	Intron 12 of 45	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9	c.2986-15C>T		intron_variant	Intron 12 of 45	1	NM_001009944.3	ENSP00000262304.4

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4461 AN: 152204 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0249

GnomAD2 exomes AF: 0.0553 AC: 13227 AN: 239304 AF XY: 0.0594

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.0435

Gnomad ASJ exome AF: 0.0143

Gnomad EAS exome AF: 0.235

Gnomad FIN exome AF: 0.00657

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0388

GnomAD4 exome AF: 0.0296 AC: 42663 AN: 1443284 Hom.: 2505 Cov.: 33 AF XY: 0.0331 AC XY: 23798 AN XY: 718578

African (AFR) AF: 0.0232 AC: 774 AN: 33354

American (AMR) AF: 0.0430 AC: 1923 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 356 AN: 26116

East Asian (EAS) AF: 0.199 AC: 7884 AN: 39676

South Asian (SAS) AF: 0.162 AC: 13979 AN: 86122

European-Finnish (FIN) AF: 0.00701 AC: 275 AN: 39246

Middle Eastern (MID) AF: 0.0283 AC: 117 AN: 4132

European-Non Finnish (NFE) AF: 0.0133 AC: 14798 AN: 1109886

Other (OTH) AF: 0.0426 AC: 2557 AN: 60052

GnomAD4 genome AF: 0.0294 AC: 4482 AN: 152322 Hom.: 249 Cov.: 32 AF XY: 0.0321 AC XY: 2393 AN XY: 74474

African (AFR) AF: 0.0221 AC: 920 AN: 41558

American (AMR) AF: 0.0311 AC: 476 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1177 AN: 5184

South Asian (SAS) AF: 0.171 AC: 827 AN: 4824

European-Finnish (FIN) AF: 0.00612 AC: 65 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 886 AN: 68028

Other (OTH) AF: 0.0346 AC: 73 AN: 2112

Alfa AF: 0.00826 Hom.: 9

Bravo AF: 0.0291

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

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

- -

Polycystic kidney disease, adult type Benign:1

Feb 20, 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.2986-15C>T, p.? variant was identified in 5.3% of 6391 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

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.025
DANN	Benign	0.72
PhyloP100		-0.57
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4
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: rs2855349; hg19: chr16-2162979; COSMIC: COSV51915841; COSMIC: COSV51915841;