16-81215111-C-T

Variant names:

• chr16-81215111-C-T
• rs12933806
• ENST00000525539.5:c.547G>A

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.547G>A​(p.Val183Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,607,898 control chromosomes in the GnomAD database, including 41,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 0.21 (3498 hom., cov: 31)
  • Exomes 𝑓: 0.23 (38475 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 26 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=0.0045801103).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525539.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	NR_126532.3		n.571G>A		non_coding_transcript_exon	Exon 3 of 43

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.547G>A	p.Val183Ile	missense	Exon 3 of 43	ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31717 AN: 151944 Hom.: 3498 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.233 AC: 55380 AN: 237516 AF XY: 0.231

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.357

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.226 AC: 329127 AN: 1455836 Hom.: 38475 Cov.: 33 AF XY: 0.227 AC XY: 163977 AN XY: 723740

African (AFR) AF: 0.157 AC: 5252 AN: 33410

American (AMR) AF: 0.232 AC: 10139 AN: 43660

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5456 AN: 25962

East Asian (EAS) AF: 0.386 AC: 15238 AN: 39492

South Asian (SAS) AF: 0.244 AC: 20752 AN: 85022

European-Finnish (FIN) AF: 0.283 AC: 14947 AN: 52834

Middle Eastern (MID) AF: 0.112 AC: 645 AN: 5766

European-Non Finnish (NFE) AF: 0.220 AC: 243603 AN: 1109532

Other (OTH) AF: 0.218 AC: 13095 AN: 60158

GnomAD4 genome AF: 0.209 AC: 31729 AN: 152062 Hom.: 3498 Cov.: 31 AF XY: 0.211 AC XY: 15646 AN XY: 74312

African (AFR) AF: 0.161 AC: 6678 AN: 41478

American (AMR) AF: 0.195 AC: 2977 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1898 AN: 5156

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4814

European-Finnish (FIN) AF: 0.271 AC: 2870 AN: 10580

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14729 AN: 67982

Other (OTH) AF: 0.182 AC: 383 AN: 2108

Alfa AF: 0.211 Hom.: 16185

Bravo AF: 0.200

TwinsUK AF: 0.220 AC: 816

ALSPAC AF: 0.216 AC: 832

ESP6500AA AF: 0.148 AC: 584

ESP6500EA AF: 0.215 AC: 1779

ExAC AF: 0.227 AC: 27454

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.79
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.56
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.058
Polyphen		0.0010	B
Vest4		0.030
ClinPred		0.013	T
GERP RS		-9.5
Mutation Taster		=98/2	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: rs12933806; hg19: chr16-81248716; COSMIC: COSV61417739;