16-81215140-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000525539.5(PKD1L2):​c.518T>A​(p.Leu173*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000354 in 1,608,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: PKD1L2 ENST00000525539.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.542T>A		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>A	p.Leu173*	stop_gained	Exon 3 of 43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151792 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000143 AC: 34 AN: 238148 Hom.: 0 AF XY: 0.000162 AC XY: 21 AN XY: 129576

Gnomad AFR exome AF: 0.0000720

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00133

Gnomad SAS exome AF: 0.0000340

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000740

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000343 AC: 50 AN: 1456660 Hom.: 0 Cov.: 38 AF XY: 0.0000318 AC XY: 23 AN XY: 724156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000278

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.0000664

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151792 Hom.: 0 Cov.: 31 AF XY: 0.0000809 AC XY: 6 AN XY: 74134

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00

ExAC AF: 0.000132 AC: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	43
DANN	Uncertain	0.98
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.58	D
Vest4		0.20
GERP RS		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8060294; hg19: chr16-81248745;