16-81215330-T-G

Position:

• chr16-81215330-T-G

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.464-136A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 795,264 control chromosomes in the GnomAD database, including 52,605 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 0.39 (12068 hom., cov: 30)
  • Exomes 𝑓: 0.35 (40537 hom.)
• Consequence: PKD1L2 ENST00000525539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L2	NR_126532.3	n.488-136A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L2	ENST00000525539.5	c.464-136A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58678 AN: 151528 Hom.: 12055 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.348 AC: 223889 AN: 643618 Hom.: 40537 AF XY: 0.345 AC XY: 112308 AN XY: 325186

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.387 AC: 58754 AN: 151646 Hom.: 12068 Cov.: 30 AF XY: 0.386 AC XY: 28602 AN XY: 74110

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.347

Alfa AF: 0.337 Hom.: 18366

Bravo AF: 0.394

Asia WGS AF: 0.411 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.32

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: rs8044334; hg19: chr16-81248935;