16-81170520-C-G

Position:

• chr16-81170520-C-G

Variant summary

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

The ENST00000531391(PKD1L2):​c.*220G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,361,450 control chromosomes in the GnomAD database, including 332,643 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 0.71 (38140 hom., cov: 31)
  • Exomes 𝑓: 0.70 (294503 hom.)
• Consequence: PKD1L2 ENST00000531391 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.2925+423G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.2910+423G>C		intron_variant		1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107472 AN: 151798 Hom.: 38106 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.700

GnomAD4 exome AF: 0.697 AC: 843160 AN: 1209534 Hom.: 294503 Cov.: 34 AF XY: 0.697 AC XY: 404142 AN XY: 579858

Gnomad4 AFR exome AF: 0.682

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.704

Gnomad4 FIN exome AF: 0.748

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.696

GnomAD4 genome AF: 0.708 AC: 107563 AN: 151916 Hom.: 38140 Cov.: 31 AF XY: 0.713 AC XY: 52907 AN XY: 74248

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.702

Alfa AF: 0.689 Hom.: 4312

Bravo AF: 0.711

Asia WGS AF: 0.744 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.1
DANN	Benign	0.70

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: rs1901818; hg19: chr16-81204125;