16-81179773-A-G

Variant names:

• chr16-81179773-A-G
• rs4889261
• ENST00000525539.5:c.2132T>C

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.2132T>C​(p.Leu711Pro) variant causes a missense change. The variant allele was found at a frequency of 0.825 in 1,613,554 control chromosomes in the GnomAD database, including 550,541 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 0.80 (49203 hom., cov: 31)
  • Exomes 𝑓: 0.83 (501338 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 32 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=8.4988994E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.2147T>C		non_coding_transcript_exon_variant	Exon 13 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.2132T>C	p.Leu711Pro	missense_variant	Exon 13 of 43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121775 AN: 151936 Hom.: 49174 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.811

GnomAD2 exomes AF: 0.821 AC: 204488 AN: 249036 AF XY: 0.821

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.822

Gnomad EAS exome AF: 0.964

Gnomad FIN exome AF: 0.857

Gnomad NFE exome AF: 0.833

Gnomad OTH exome AF: 0.820

GnomAD4 exome AF: 0.827 AC: 1208980 AN: 1461500 Hom.: 501338 Cov.: 58 AF XY: 0.826 AC XY: 600393 AN XY: 727040

African (AFR) AF: 0.720 AC: 24095 AN: 33468

American (AMR) AF: 0.800 AC: 35729 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 21350 AN: 26130

East Asian (EAS) AF: 0.966 AC: 38350 AN: 39694

South Asian (SAS) AF: 0.758 AC: 65399 AN: 86228

European-Finnish (FIN) AF: 0.859 AC: 45839 AN: 53390

Middle Eastern (MID) AF: 0.817 AC: 4712 AN: 5768

European-Non Finnish (NFE) AF: 0.831 AC: 923912 AN: 1111764

Other (OTH) AF: 0.821 AC: 49594 AN: 60376

GnomAD4 genome AF: 0.801 AC: 121854 AN: 152054 Hom.: 49203 Cov.: 31 AF XY: 0.803 AC XY: 59693 AN XY: 74330

African (AFR) AF: 0.721 AC: 29855 AN: 41436

American (AMR) AF: 0.800 AC: 12225 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2807 AN: 3472

East Asian (EAS) AF: 0.966 AC: 4988 AN: 5164

South Asian (SAS) AF: 0.752 AC: 3621 AN: 4816

European-Finnish (FIN) AF: 0.855 AC: 9052 AN: 10582

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56541 AN: 67988

Other (OTH) AF: 0.810 AC: 1710 AN: 2112

Alfa AF: 0.824 Hom.: 184097

Bravo AF: 0.800

TwinsUK AF: 0.835 AC: 3098

ALSPAC AF: 0.826 AC: 3185

ESP6500AA AF: 0.728 AC: 2840

ESP6500EA AF: 0.835 AC: 6931

ExAC AF: 0.819 AC: 98980

Asia WGS AF: 0.843 AC: 2929 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.12
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.14	T;T;T
MetaRNN	Benign	8.5e-7	T;T;T
MetaSVM	Benign	-0.94	T
PhyloP100		3.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	4.5	N;N;N
REVEL	Benign	0.26
Polyphen		0.0	.;B;B
Vest4		0.18
MPC		.;.;4.19142513741E-4
ClinPred		0.0036	T
GERP RS		5.0
Mutation Taster		=89/11	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: rs4889261; hg19: chr16-81213378; COSMIC: COSV55167098;