rs9924530

Variant names:

• chr16-81220312-A-G
• rs9924530
• ENST00000525539.5:c.59T>C

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.59T>C​(p.Val20Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,613,564 control chromosomes in the GnomAD database, including 300,370 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 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 0.61 (28377 hom., cov: 32)
  • Exomes 𝑓: 0.61 (271993 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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=1.08696E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.83T>C		non_coding_transcript_exon_variant	Exon 1 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.59T>C	p.Val20Ala	missense_variant	Exon 1 of 43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92309 AN: 151758 Hom.: 28355 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.617

GnomAD3 exomes AF: 0.565 AC: 140406 AN: 248354 Hom.: 40776 AF XY: 0.564 AC XY: 76020 AN XY: 134872

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.483

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.412

Gnomad SAS exome AF: 0.421

Gnomad FIN exome AF: 0.601

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.610

GnomAD4 exome AF: 0.606 AC: 885591 AN: 1461690 Hom.: 271993 Cov.: 67 AF XY: 0.601 AC XY: 436951 AN XY: 727152

Gnomad4 AFR exome AF: 0.620

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.633

Gnomad4 OTH exome AF: 0.598

GnomAD4 genome AF: 0.608 AC: 92378 AN: 151874 Hom.: 28377 Cov.: 32 AF XY: 0.602 AC XY: 44659 AN XY: 74228

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.613

Alfa AF: 0.621 Hom.: 26198

Bravo AF: 0.608

TwinsUK AF: 0.633 AC: 2346

ALSPAC AF: 0.636 AC: 2451

ESP6500AA AF: 0.645 AC: 2630

ESP6500EA AF: 0.631 AC: 5299

ExAC AF: 0.568 AC: 68602

Asia WGS AF: 0.491 AC: 1708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.0
DANN	Benign	0.12
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.020
Polyphen		0.0	B
Vest4		0.025
ClinPred		0.0076	T
GERP RS		3.2

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: rs9924530; hg19: chr16-81253917; COSMIC: COSV61413270;