rs149879790

Variant names:

• chr16-2104550-G-A
• rs149879790
• NM_001009944.3:c.8109C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2104550-G-A
• chr16-2104550-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001009944.3(PKD1):​c.8109C>T​(p.Thr2703Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,591,226 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 20)
  • Exomes 𝑓: 0.00095 (9 hom.)
• Consequence: PKD1 NM_001009944.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.87
• Publications: 0 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: Orphanet, ClinGen
• 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=-0.89).
• BP6: Variant 16-2104550-G-A is Benign according to our data. Variant chr16-2104550-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.87 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00375 (563/150032) while in subpopulation AFR AF = 0.0105 (425/40436). AF 95% confidence interval is 0.00969. There are 4 homozygotes in GnomAd4. There are 285 alleles in the male GnomAd4 subpopulation. Median coverage is 20. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.8109C>T	p.Thr2703Thr	synonymous	Exon 22 of 46	NP_001009944.3	P98161-1
	PKD1	NM_000296.4		c.8109C>T	p.Thr2703Thr	synonymous	Exon 22 of 46	NP_000287.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.8109C>T	p.Thr2703Thr	synonymous	Exon 22 of 46	ENSP00000262304.4	P98161-1
	PKD1	ENST00000423118.5	TSL:1	c.8109C>T	p.Thr2703Thr	synonymous	Exon 22 of 46	ENSP00000399501.1	P98161-3
	PKD1	ENST00000567946.1	TSL:5	c.168C>T	p.Thr56Thr	synonymous	Exon 2 of 12	ENSP00000457984.1	H3BV77

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 564 AN: 149914 Hom.: 4 Cov.: 20

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00139

Gnomad ASJ AF: 0.000868

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.00599

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000607

Gnomad OTH AF: 0.00387

GnomAD2 exomes AF: 0.00135 AC: 213 AN: 157772 AF XY: 0.00124

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000428

Gnomad ASJ exome AF: 0.000946

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00480

Gnomad NFE exome AF: 0.000608

Gnomad OTH exome AF: 0.000903

GnomAD4 exome AF: 0.000949 AC: 1368 AN: 1441194 Hom.: 9 Cov.: 30 AF XY: 0.000938 AC XY: 672 AN XY: 716124

African (AFR) AF: 0.0130 AC: 429 AN: 33100

American (AMR) AF: 0.000508 AC: 22 AN: 43268

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 26 AN: 25764

East Asian (EAS) AF: 0.000204 AC: 8 AN: 39240

South Asian (SAS) AF: 0.000262 AC: 22 AN: 83928

European-Finnish (FIN) AF: 0.00466 AC: 231 AN: 49620

Middle Eastern (MID) AF: 0.00341 AC: 14 AN: 4110

European-Non Finnish (NFE) AF: 0.000480 AC: 529 AN: 1102588

Other (OTH) AF: 0.00146 AC: 87 AN: 59576

GnomAD4 genome AF: 0.00375 AC: 563 AN: 150032 Hom.: 4 Cov.: 20 AF XY: 0.00389 AC XY: 285 AN XY: 73232

African (AFR) AF: 0.0105 AC: 425 AN: 40436

American (AMR) AF: 0.00139 AC: 21 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.000868 AC: 3 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 4952

South Asian (SAS) AF: 0.000425 AC: 2 AN: 4708

European-Finnish (FIN) AF: 0.00599 AC: 63 AN: 10518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000607 AC: 41 AN: 67546

Other (OTH) AF: 0.00383 AC: 8 AN: 2088

Alfa AF: 0.000612 Hom.: 0

Bravo AF: 0.00398

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Polycystic kidney disease (1)
-	-	1	Polycystic kidney disease, adult type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.92
DANN	Benign	0.77
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism

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: rs149879790; hg19: chr16-2154551;