chr16-81215140-A-G

Variant names:

• chr16-81215140-A-G
• rs8060294
• ENST00000525539.5:c.518T>C

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.518T>C​(p.Leu173Ser) variant causes a missense change. The variant allele was found at a frequency of 0.309 in 1,608,088 control chromosomes in the GnomAD database, including 79,704 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 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 0.36 (10644 hom., cov: 31)
  • Exomes 𝑓: 0.30 (69060 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33
• Publications: 24 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=6.0650706E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.542T>C		non_coding_transcript_exon_variant	Exon 3 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.518T>C	p.Leu173Ser	missense_variant	Exon 3 of 43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54451 AN: 151730 Hom.: 10632 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.320

GnomAD2 exomes AF: 0.306 AC: 72906 AN: 238148 AF XY: 0.299

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.412

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.301

GnomAD4 exome AF: 0.304 AC: 442713 AN: 1456240 Hom.: 69060 Cov.: 38 AF XY: 0.301 AC XY: 217593 AN XY: 723950

African (AFR) AF: 0.531 AC: 17683 AN: 33304

American (AMR) AF: 0.311 AC: 13627 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5529 AN: 25988

East Asian (EAS) AF: 0.389 AC: 15353 AN: 39514

South Asian (SAS) AF: 0.266 AC: 22655 AN: 85158

European-Finnish (FIN) AF: 0.307 AC: 16213 AN: 52850

Middle Eastern (MID) AF: 0.247 AC: 1424 AN: 5756

European-Non Finnish (NFE) AF: 0.298 AC: 331181 AN: 1109738

Other (OTH) AF: 0.317 AC: 19048 AN: 60176

GnomAD4 genome AF: 0.359 AC: 54527 AN: 151848 Hom.: 10644 Cov.: 31 AF XY: 0.358 AC XY: 26562 AN XY: 74226

African (AFR) AF: 0.522 AC: 21590 AN: 41350

American (AMR) AF: 0.322 AC: 4913 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3468

East Asian (EAS) AF: 0.402 AC: 2074 AN: 5158

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4814

European-Finnish (FIN) AF: 0.326 AC: 3448 AN: 10566

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19472 AN: 67930

Other (OTH) AF: 0.320 AC: 675 AN: 2108

Alfa AF: 0.302 Hom.: 26566

Bravo AF: 0.371

TwinsUK AF: 0.307 AC: 1138

ALSPAC AF: 0.306 AC: 1180

ESP6500AA AF: 0.507 AC: 1980

ESP6500EA AF: 0.278 AC: 2300

ExAC AF: 0.300 AC: 36191

Asia WGS AF: 0.407 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.97
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.00061	T
MetaSVM	Benign	-0.93	T
PhyloP100		5.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.11
Polyphen		0.0	B
Vest4		0.15
ClinPred		0.0067	T
GERP RS		3.8
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: rs8060294; hg19: chr16-81248745; COSMIC: COSV61412754;