chr16-81198670-G-A

Position:

• chr16-81198670-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000525539.5(PKD1L2):​c.1535C>T​(p.Pro512Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,613,156 control chromosomes in the GnomAD database, including 502,089 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P512T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.76 (44155 hom., cov: 32)
  • Exomes 𝑓: 0.79 (457934 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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]

PKD1L2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.383563E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.1550C>T		non_coding_transcript_exon_variant	7/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.1535C>T	p.Pro512Leu	missense_variant	7/43	1		ENSP00000434417.1
PKD1L2	ENST00000526632.5	c.116C>T	p.Pro39Leu	missense_variant	1/12	2		ENSP00000436389.1
PKD1L2	ENST00000710634.1	n.149C>T		non_coding_transcript_exon_variant	1/10			ENSP00000518389.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115111 AN: 151952 Hom.: 44148 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.742

GnomAD3 exomes AF: 0.791 AC: 196561 AN: 248588 Hom.: 78365 AF XY: 0.790 AC XY: 106486 AN XY: 134874

Gnomad AFR exome AF: 0.644

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.786

Gnomad EAS exome AF: 0.958

Gnomad SAS exome AF: 0.724

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.794

Gnomad OTH exome AF: 0.792

GnomAD4 exome AF: 0.790 AC: 1154960 AN: 1461086 Hom.: 457934 Cov.: 68 AF XY: 0.789 AC XY: 573524 AN XY: 726772

Gnomad4 AFR exome AF: 0.649

Gnomad4 AMR exome AF: 0.794

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.829

Gnomad4 NFE exome AF: 0.793

Gnomad4 OTH exome AF: 0.780

GnomAD4 genome AF: 0.757 AC: 115148 AN: 152070 Hom.: 44155 Cov.: 32 AF XY: 0.760 AC XY: 56497 AN XY: 74352

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.737

Alfa AF: 0.791 Hom.: 106592

Bravo AF: 0.754

TwinsUK AF: 0.797 AC: 2955

ALSPAC AF: 0.789 AC: 3040

ESP6500AA AF: 0.664 AC: 2650

ESP6500EA AF: 0.793 AC: 6579

ExAC AF: 0.786 AC: 95012

Asia WGS AF: 0.809 AC: 2812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.53	T
MetaRNN	Benign	9.4e-7	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.22
Polyphen		1.0	D
Vest4		0.40
ClinPred		0.048	T
GERP RS		5.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7205673; hg19: chr16-81232275;