ENST00000525539.5:c.2353G>T

Variant names:

• chr16-81177891-C-A
• rs9935113
• ENST00000525539.5:c.2353G>T

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.2353G>T​(p.Gly785Cys) variant causes a missense change. The variant allele was found at a frequency of 0.18 in 1,613,554 control chromosomes in the GnomAD database, including 27,320 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 0.20 (3148 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24172 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.19
• Publications: 25 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=0.001959771).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 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.2368G>T		non_coding_transcript_exon	Exon 14 of 43

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.2353G>T	p.Gly785Cys	missense	Exon 14 of 43	ENSP00000434417.1
	PKD1L2	ENST00000533478.5	TSL:1	c.298G>T	p.Gly100Cys	missense	Exon 3 of 32	ENSP00000434644.1
	PKD1L2	ENST00000531391.5	TSL:1	c.298G>T	p.Gly100Cys	missense	Exon 3 of 7	ENSP00000436309.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29723 AN: 151780 Hom.: 3138 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.184 AC: 45775 AN: 248896 AF XY: 0.185

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.107

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.178 AC: 259960 AN: 1461656 Hom.: 24172 Cov.: 32 AF XY: 0.179 AC XY: 130391 AN XY: 727140

African (AFR) AF: 0.257 AC: 8597 AN: 33478

American (AMR) AF: 0.199 AC: 8892 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 4706 AN: 26114

East Asian (EAS) AF: 0.0747 AC: 2965 AN: 39694

South Asian (SAS) AF: 0.251 AC: 21651 AN: 86242

European-Finnish (FIN) AF: 0.142 AC: 7596 AN: 53374

Middle Eastern (MID) AF: 0.182 AC: 1048 AN: 5748

European-Non Finnish (NFE) AF: 0.174 AC: 193337 AN: 1111924

Other (OTH) AF: 0.185 AC: 11168 AN: 60382

GnomAD4 genome AF: 0.196 AC: 29754 AN: 151898 Hom.: 3148 Cov.: 31 AF XY: 0.194 AC XY: 14364 AN XY: 74232

African (AFR) AF: 0.258 AC: 10673 AN: 41386

American (AMR) AF: 0.196 AC: 2990 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3472

East Asian (EAS) AF: 0.0980 AC: 504 AN: 5142

South Asian (SAS) AF: 0.259 AC: 1245 AN: 4808

European-Finnish (FIN) AF: 0.143 AC: 1511 AN: 10572

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11621 AN: 67928

Other (OTH) AF: 0.189 AC: 399 AN: 2106

Alfa AF: 0.175 Hom.: 10985

Bravo AF: 0.197

TwinsUK AF: 0.169 AC: 628

ALSPAC AF: 0.179 AC: 690

ESP6500AA AF: 0.247 AC: 1011

ESP6500EA AF: 0.168 AC: 1412

ExAC AF: 0.185 AC: 22322

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	0.084
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.2
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Pathogenic	0.71
Polyphen		1.0	D
Vest4		0.82
ClinPred		0.092	T
GERP RS		4.9
Mutation Taster		=74/26	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: rs9935113; hg19: chr16-81211496; COSMIC: COSV55162211;