chr16-81198959-T-G

Position:

• chr16-81198959-T-G

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.1246A>C​(p.Lys416Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,613,990 control chromosomes in the GnomAD database, including 511,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 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 0.78 (46783 hom., cov: 32)
  • Exomes 𝑓: 0.80 (465137 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505

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=7.017998E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.1261A>C		non_coding_transcript_exon_variant	7/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.1246A>C	p.Lys416Gln	missense_variant	7/43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118818 AN: 151998 Hom.: 46762 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.760

GnomAD3 exomes AF: 0.799 AC: 199446 AN: 249552 Hom.: 80218 AF XY: 0.797 AC XY: 107924 AN XY: 135394

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.799

Gnomad ASJ exome AF: 0.792

Gnomad EAS exome AF: 0.961

Gnomad SAS exome AF: 0.728

Gnomad FIN exome AF: 0.830

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.798

GnomAD4 exome AF: 0.797 AC: 1164772 AN: 1461876 Hom.: 465137 Cov.: 73 AF XY: 0.795 AC XY: 578308 AN XY: 727240

Gnomad4 AFR exome AF: 0.734

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.784

Gnomad4 EAS exome AF: 0.962

Gnomad4 SAS exome AF: 0.731

Gnomad4 FIN exome AF: 0.830

Gnomad4 NFE exome AF: 0.797

Gnomad4 OTH exome AF: 0.790

GnomAD4 genome AF: 0.782 AC: 118883 AN: 152114 Hom.: 46783 Cov.: 32 AF XY: 0.783 AC XY: 58249 AN XY: 74362

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.755

Alfa AF: 0.797 Hom.: 120971

Bravo AF: 0.782

TwinsUK AF: 0.801 AC: 2970

ALSPAC AF: 0.792 AC: 3052

ESP6500AA AF: 0.741 AC: 2905

ESP6500EA AF: 0.796 AC: 6605

ExAC AF: 0.796 AC: 96239

Asia WGS AF: 0.827 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.71
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	7.0e-7	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.021
Polyphen		0.0020	B
Vest4		0.053
ClinPred		0.0048	T
GERP RS		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs7194871; hg19: chr16-81232564;