chr16-81216322-C-T

Variant names:

• chr16-81216322-C-T
• rs7185774
• ENST00000525539.5:c.386G>A

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.386G>A​(p.Gly129Asp) variant causes a missense change. The variant allele was found at a frequency of 0.298 in 1,613,732 control chromosomes in the GnomAD database, including 78,090 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 0.25 (5902 hom., cov: 33)
  • Exomes 𝑓: 0.30 (72188 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• Publications: 19 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 (MetaRNN=0.0021229684).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.410G>A		non_coding_transcript_exon_variant	Exon 2 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.386G>A	p.Gly129Asp	missense_variant	Exon 2 of 43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38478 AN: 152024 Hom.: 5905 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.00734

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.260 AC: 64940 AN: 249314 AF XY: 0.266

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.00590

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.303 AC: 442269 AN: 1461590 Hom.: 72188 Cov.: 52 AF XY: 0.301 AC XY: 218840 AN XY: 727094

African (AFR) AF: 0.103 AC: 3434 AN: 33478

American (AMR) AF: 0.186 AC: 8297 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9825 AN: 26118

East Asian (EAS) AF: 0.00300 AC: 119 AN: 39700

South Asian (SAS) AF: 0.155 AC: 13390 AN: 86224

European-Finnish (FIN) AF: 0.295 AC: 15715 AN: 53354

Middle Eastern (MID) AF: 0.421 AC: 2428 AN: 5768

European-Non Finnish (NFE) AF: 0.334 AC: 371854 AN: 1111844

Other (OTH) AF: 0.285 AC: 17207 AN: 60384

GnomAD4 genome AF: 0.253 AC: 38470 AN: 152142 Hom.: 5902 Cov.: 33 AF XY: 0.248 AC XY: 18433 AN XY: 74400

African (AFR) AF: 0.112 AC: 4649 AN: 41512

American (AMR) AF: 0.252 AC: 3846 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3466

East Asian (EAS) AF: 0.00736 AC: 38 AN: 5164

South Asian (SAS) AF: 0.151 AC: 729 AN: 4832

European-Finnish (FIN) AF: 0.288 AC: 3050 AN: 10596

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23769 AN: 67966

Other (OTH) AF: 0.298 AC: 628 AN: 2110

Alfa AF: 0.309 Hom.: 17791

Bravo AF: 0.244

TwinsUK AF: 0.326 AC: 1207

ALSPAC AF: 0.329 AC: 1269

ESP6500AA AF: 0.116 AC: 481

ESP6500EA AF: 0.346 AC: 2910

ExAC AF: 0.263 AC: 31796

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.3
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.28
Polyphen		1.0	D
Vest4		0.79
ClinPred		0.015	T
GERP RS		5.1
Mutation Taster		=58/42	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7185774; hg19: chr16-81249927; COSMIC: COSV61417677;