16-81170520-C-G

Variant names:

• chr16-81170520-C-G
• rs1901818
• ENST00000531391.5:c.*220G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000531391.5(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 ENST00000531391.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.2925+423G>C		intron_variant	Intron 17 of 42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.2910+423G>C		intron_variant	Intron 17 of 42	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

African (AFR) AF: 0.682 AC: 18126 AN: 26590

American (AMR) AF: 0.802 AC: 11385 AN: 14192

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 11222 AN: 17298

East Asian (EAS) AF: 0.698 AC: 21728 AN: 31118

South Asian (SAS) AF: 0.704 AC: 32532 AN: 46224

European-Finnish (FIN) AF: 0.748 AC: 21667 AN: 28970

Middle Eastern (MID) AF: 0.628 AC: 2111 AN: 3362

European-Non Finnish (NFE) AF: 0.695 AC: 689631 AN: 991818

Other (OTH) AF: 0.696 AC: 34758 AN: 49962

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

African (AFR) AF: 0.689 AC: 28491 AN: 41378

American (AMR) AF: 0.787 AC: 12018 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2236 AN: 3468

East Asian (EAS) AF: 0.707 AC: 3627 AN: 5130

South Asian (SAS) AF: 0.721 AC: 3474 AN: 4818

European-Finnish (FIN) AF: 0.775 AC: 8193 AN: 10578

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47236 AN: 67960

Other (OTH) AF: 0.702 AC: 1484 AN: 2114

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
PhyloP100		-0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1901818; hg19: chr16-81204125;