rs9935113

chr16-81177891-C-A

Variant summary

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

The ENST00000531391.5(PKD1L2):c.298G>T(p.Gly100Cys) variant causes a missense change. The variant allele was found at a frequency of 0.18 in 1,613,554 control chromosomes in the GnomAD database, including 27,320 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 0.20 (3148 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24172 hom.)
• Consequence: PKD1L2 ENST00000531391.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19

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=0.001959771).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L2	NR_126532.3	n.2368G>T		non_coding_transcript_exon_variant	14/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L2	ENST00000525539.5	c.2353G>T	p.Gly785Cys	missense_variant	14/43	1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29723 AN: 151780 Hom.: 3138 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.184 AC: 45775 AN: 248896 Hom.: 4570 AF XY: 0.185 AC XY: 24925 AN XY: 135094

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.107

Gnomad SAS exome AF: 0.257

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.178 AC: 259960 AN: 1461656 Hom.: 24172 Cov.: 32 AF XY: 0.179 AC XY: 130391 AN XY: 727140

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.0747

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.196 AC: 29754 AN: 151898 Hom.: 3148 Cov.: 31 AF XY: 0.194 AC XY: 14364 AN XY: 74232

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0980

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.189

Alfa AF: 0.172 Hom.: 5764

Bravo AF: 0.197

TwinsUK AF: 0.169 AC: 628

ALSPAC AF: 0.179 AC: 690

ESP6500AA AF: 0.247 AC: 1011

ESP6500EA AF: 0.168 AC: 1412

ExAC AF: 0.185 AC: 22322

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Uncertain	0.020
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	0.084
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.75	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.63	P;P;P
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-8.2	D;D
REVEL	Pathogenic	0.71
Polyphen		1.0	.;D
Vest4		0.82
ClinPred		0.092	T
GERP RS		4.9

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: rs9935113; hg19: chr16-81211496; COSMIC: COSV55162211;