rs569511

chr10-100329906-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016112.3(PKD2L1):c.198G>A(p.Val66=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,612,588 control chromosomes in the GnomAD database, including 16,645 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1326 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15319 hom.)
• Consequence: PKD2L1 NM_016112.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

Genes affected

PKD2L1 (HGNC:9011): (polycystin 2 like 1, transient receptor potential cation channel) This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-0.224 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD2L1	NM_016112.3	c.198G>A	p.Val66=	synonymous_variant	1/16	ENST00000318222.4
PKD2L1	NM_001253837.2	c.35G>A	p.Cys12Tyr	missense_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD2L1	ENST00000318222.4	c.198G>A	p.Val66=	synonymous_variant	1/16	1	NM_016112.3	P1
PKD2L1	ENST00000528248.1	c.36G>A	p.Val12=	synonymous_variant, NMD_transcript_variant	1/16	1
PKD2L1	ENST00000465680.2	c.69G>A	p.Val23=	synonymous_variant	1/2	3
PKD2L1	ENST00000532547.1	c.195+3G>A		splice_donor_region_variant, intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18588 AN: 152100 Hom.: 1323 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.138 AC: 34715 AN: 250700 Hom.: 3214 AF XY: 0.151 AC XY: 20456 AN XY: 135494

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.0356

Gnomad SAS exome AF: 0.313

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.135 AC: 196529 AN: 1460370 Hom.: 15319 Cov.: 31 AF XY: 0.141 AC XY: 102351 AN XY: 726514

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0712

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.0263

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.122 AC: 18603 AN: 152218 Hom.: 1326 Cov.: 32 AF XY: 0.123 AC XY: 9172 AN XY: 74416

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.130

Alfa AF: 0.130 Hom.: 752

Bravo AF: 0.118

Asia WGS AF: 0.196 AC: 682 AN: 3478

EpiCase AF: 0.138

EpiControl AF: 0.148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	13
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.59		Position offset: 3
DS_DL_spliceai		0.25		Position offset: -37

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs569511; hg19: chr10-102089663; COSMIC: COSV58399802;