16-81198959-T-G

Variant names:

• chr16-81198959-T-G
• rs7194871
• ENST00000525539.5:c.1246A>C

Variant summary

Our verdict is Benign. The variant received -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. 14/18 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
• Publications: 26 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=7.017998E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 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.1261A>C		non_coding_transcript_exon	Exon 7 of 43

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1L2	ENST00000525539.5	TSL:1	c.1246A>C	p.Lys416Gln	missense	Exon 7 of 43	ENSP00000434417.1
	PKD1L2	ENST00000526632.5	TSL:2	c.-174A>C		upstream_gene	N/A	ENSP00000436389.1
	PKD1L2	ENST00000710634.1		n.-141A>C		upstream_gene	N/A	ENSP00000518389.1

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

GnomAD2 exomes AF: 0.799 AC: 199446 AN: 249552 AF XY: 0.797

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 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

African (AFR) AF: 0.734 AC: 24579 AN: 33480

American (AMR) AF: 0.799 AC: 35734 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 20478 AN: 26136

East Asian (EAS) AF: 0.962 AC: 38172 AN: 39700

South Asian (SAS) AF: 0.731 AC: 63068 AN: 86256

European-Finnish (FIN) AF: 0.830 AC: 44318 AN: 53418

Middle Eastern (MID) AF: 0.803 AC: 4634 AN: 5768

European-Non Finnish (NFE) AF: 0.797 AC: 886089 AN: 1111998

Other (OTH) AF: 0.790 AC: 47700 AN: 60396

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

African (AFR) AF: 0.731 AC: 30327 AN: 41472

American (AMR) AF: 0.780 AC: 11914 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2694 AN: 3472

East Asian (EAS) AF: 0.963 AC: 4975 AN: 5168

South Asian (SAS) AF: 0.722 AC: 3481 AN: 4824

European-Finnish (FIN) AF: 0.832 AC: 8809 AN: 10592

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54131 AN: 68006

Other (OTH) AF: 0.755 AC: 1592 AN: 2108

Alfa AF: 0.795 Hom.: 159915

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
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
PhyloP100		0.51
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
PromoterAI		-0.010	Neutral
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: rs7194871; hg19: chr16-81232564; COSMIC: COSV107419793; COSMIC: COSV107419793;