rs8060294

chr16-81215140-A-Gchr16-81215140-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000525539.5(PKD1L2):c.518T>C(p.Leu173Ser) variant causes a missense change. The variant allele was found at a frequency of 0.309 in 1,608,088 control chromosomes in the GnomAD database, including 79,704 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10644 hom., cov: 31)
  • Exomes 𝑓: 0.30 (69060 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33

Genes affected

PKD1L2 (HGNC:21715): (polycystin 1 like 2 (gene/pseudogene)) This gene encodes a member of the polycystin protein family. This protein may function as a G-protein-coupled component or regulator of cation channel pores. The long isoform of this protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene is a polymorphic pseudogene in humans. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0650706E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L2	NR_126532.3	n.542T>C		non_coding_transcript_exon_variant	3/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L2	ENST00000525539.5	c.518T>C	p.Leu173Ser	missense_variant	3/43	1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54451 AN: 151730 Hom.: 10632 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.320

GnomAD3 exomes AF: 0.306 AC: 72906 AN: 238148 Hom.: 11689 AF XY: 0.299 AC XY: 38694 AN XY: 129576

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.412

Gnomad SAS exome AF: 0.269

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.304 AC: 442713 AN: 1456240 Hom.: 69060 Cov.: 38 AF XY: 0.301 AC XY: 217593 AN XY: 723950

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.359 AC: 54527 AN: 151848 Hom.: 10644 Cov.: 31 AF XY: 0.358 AC XY: 26562 AN XY: 74226

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.320

Alfa AF: 0.285 Hom.: 11704

Bravo AF: 0.371

TwinsUK AF: 0.307 AC: 1138

ALSPAC AF: 0.306 AC: 1180

ESP6500AA AF: 0.507 AC: 1980

ESP6500EA AF: 0.278 AC: 2300

ExAC AF: 0.300 AC: 36191

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	12
Dann	Benign	0.97
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.00061	T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.96	P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.11
Polyphen		0.0	B
Vest4		0.15
ClinPred		0.0067	T
GERP RS		3.8

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

LitVar

Other links and lift over

dbSNP: rs8060294; hg19: chr16-81248745; COSMIC: COSV61412754;