rs569511

Variant names:

• chr10-100329906-C-T
• rs569511
• NM_016112.3:c.198G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_016112.3(PKD2L1):​c.198G>A​(p.Val66Val) 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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• 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 rank	MANE	Protein	UniProt
PKD2L1	NM_016112.3	c.198G>A	p.Val66Val	synonymous_variant	Exon 1 of 16	ENST00000318222.4	NP_057196.2
PKD2L1	NM_001253837.2	c.35G>A	p.Cys12Tyr	missense_variant	Exon 1 of 16		NP_001240766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD2L1	ENST00000318222.4	c.198G>A	p.Val66Val	synonymous_variant	Exon 1 of 16	1	NM_016112.3	ENSP00000325296.3
PKD2L1	ENST00000528248.1	n.33G>A		non_coding_transcript_exon_variant	Exon 1 of 16	1		ENSP00000436514.1
PKD2L1	ENST00000465680.2	c.66G>A	p.Val22Val	synonymous_variant	Exon 1 of 2	3		ENSP00000434019.1
PKD2L1	ENST00000532547.1	n.195+3G>A		splice_region_variant, intron_variant	Intron 1 of 2	4		ENSP00000434224.1

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

GnomAD2 exomes AF: 0.138 AC: 34715 AN: 250700 AF XY: 0.151

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 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

African (AFR) AF: 0.105 AC: 3528 AN: 33464

American (AMR) AF: 0.0712 AC: 3183 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5123 AN: 26100

East Asian (EAS) AF: 0.0263 AC: 1044 AN: 39694

South Asian (SAS) AF: 0.306 AC: 26392 AN: 86174

European-Finnish (FIN) AF: 0.107 AC: 5726 AN: 53416

Middle Eastern (MID) AF: 0.220 AC: 1264 AN: 5758

European-Non Finnish (NFE) AF: 0.128 AC: 141981 AN: 1110738

Other (OTH) AF: 0.137 AC: 8288 AN: 60336

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

African (AFR) AF: 0.104 AC: 4300 AN: 41534

American (AMR) AF: 0.101 AC: 1547 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3470

East Asian (EAS) AF: 0.0340 AC: 176 AN: 5184

South Asian (SAS) AF: 0.301 AC: 1455 AN: 4826

European-Finnish (FIN) AF: 0.105 AC: 1107 AN: 10586

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8870 AN: 68006

Other (OTH) AF: 0.130 AC: 275 AN: 2110

Alfa AF: 0.127 Hom.: 2240

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
PhyloP100		-0.22
PromoterAI		0.076	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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