rs6420424

Positions:

• chr16-81208497-G-A
• chr16-81208497-G-C
• chr16-81208497-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000525539.5(PKD1L2):​c.754C>T​(p.Arg252Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,551,116 control chromosomes in the GnomAD database, including 200,653 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (19071 hom., cov: 33)
  • Exomes 𝑓: 0.50 (181582 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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]

PKD1L2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.9544905E-7).
• BP6: Variant 16-81208497-G-A is Benign according to our data. Variant chr16-81208497-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.778C>T		non_coding_transcript_exon_variant	4/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.754C>T	p.Arg252Trp	missense_variant	4/43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75011 AN: 151970 Hom.: 19051 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.446

GnomAD3 exomes AF: 0.520 AC: 128795 AN: 247542 Hom.: 35408 AF XY: 0.513 AC XY: 68880 AN XY: 134290

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.870

Gnomad SAS exome AF: 0.522

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.468

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.498 AC: 696897 AN: 1399028 Hom.: 181582 Cov.: 31 AF XY: 0.497 AC XY: 347576 AN XY: 698826

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.860

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.494 AC: 75092 AN: 152088 Hom.: 19071 Cov.: 33 AF XY: 0.497 AC XY: 36911 AN XY: 74340

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.447

Alfa AF: 0.478 Hom.: 44857

Bravo AF: 0.494

TwinsUK AF: 0.496 AC: 1841

ALSPAC AF: 0.484 AC: 1867

ESP6500AA AF: 0.443 AC: 1858

ESP6500EA AF: 0.469 AC: 3958

ExAC AF: 0.517 AC: 62512

Asia WGS AF: 0.682 AC: 2370 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	-0.53
CADD	Benign	20
DANN	Benign	0.86
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	7.0e-7	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.14
Polyphen		0.015	B
Vest4		0.19
ClinPred		0.0047	T
GERP RS		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6420424; hg19: chr16-81242102; COSMIC: COSV61415384;