chr16-81123748-G-A

Variant names:

• chr16-81123748-G-A
• rs16954698
• ENST00000525539.5:c.6386C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000525539.5(PKD1L2):​c.6386C>T​(p.Thr2129Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,613,876 control chromosomes in the GnomAD database, including 2,587 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 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 0.053 (298 hom., cov: 34)
  • Exomes 𝑓: 0.052 (2289 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 14 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.6401C>T		non_coding_transcript_exon_variant	Exon 37 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.6386C>T	p.Thr2129Met	missense_variant	Exon 37 of 43	1		ENSP00000434417.1
PKD1L2	ENST00000533478.5	c.4331C>T	p.Thr1444Met	missense_variant	Exon 26 of 32	1		ENSP00000434644.1
PKD1L2	ENST00000530363.5	n.878C>T		non_coding_transcript_exon_variant	Exon 6 of 6	1
PKD1L2	ENST00000534142.5	n.775C>T		non_coding_transcript_exon_variant	Exon 5 of 11	2

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8118 AN: 152180 Hom.: 290 Cov.: 34

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0948

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0501

GnomAD2 exomes AF: 0.0625 AC: 15587 AN: 249216 AF XY: 0.0615

Gnomad AFR exome AF: 0.0347

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0472

Gnomad EAS exome AF: 0.0427

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.0439

Gnomad OTH exome AF: 0.0610

GnomAD4 exome AF: 0.0517 AC: 75626 AN: 1461578 Hom.: 2289 Cov.: 39 AF XY: 0.0523 AC XY: 38022 AN XY: 727068

African (AFR) AF: 0.0353 AC: 1183 AN: 33474

American (AMR) AF: 0.116 AC: 5169 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0511 AC: 1336 AN: 26134

East Asian (EAS) AF: 0.0574 AC: 2280 AN: 39690

South Asian (SAS) AF: 0.0719 AC: 6200 AN: 86244

European-Finnish (FIN) AF: 0.0991 AC: 5293 AN: 53390

Middle Eastern (MID) AF: 0.0394 AC: 227 AN: 5762

European-Non Finnish (NFE) AF: 0.0457 AC: 50790 AN: 1111804

Other (OTH) AF: 0.0521 AC: 3148 AN: 60366

GnomAD4 genome AF: 0.0534 AC: 8139 AN: 152298 Hom.: 298 Cov.: 34 AF XY: 0.0579 AC XY: 4312 AN XY: 74476

African (AFR) AF: 0.0359 AC: 1492 AN: 41562

American (AMR) AF: 0.0957 AC: 1464 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3468

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5182

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0456 AC: 3104 AN: 68024

Other (OTH) AF: 0.0496 AC: 105 AN: 2116

Alfa AF: 0.0467 Hom.: 771

Bravo AF: 0.0512

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16954698; hg19: chr16-81157353;