rs7191351

Variant names:

• chr16-81216349-T-A
• rs7191351
• ENST00000525539.5:c.359A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-81216349-T-A
• chr16-81216349-T-G

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.359A>T​(p.Gln120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,613,750 control chromosomes in the GnomAD database, including 291,473 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.55 (23978 hom., cov: 33)
  • Exomes 𝑓: 0.60 (267495 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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=1.1443923E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.383A>T		non_coding_transcript_exon_variant	Exon 2 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.359A>T	p.Gln120Leu	missense_variant	Exon 2 of 43	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83940 AN: 152014 Hom.: 23971 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.585

GnomAD2 exomes AF: 0.552 AC: 137613 AN: 249172 AF XY: 0.554

Gnomad AFR exome AF: 0.420

Gnomad AMR exome AF: 0.475

Gnomad ASJ exome AF: 0.590

Gnomad EAS exome AF: 0.418

Gnomad FIN exome AF: 0.603

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.600 AC: 876936 AN: 1461618 Hom.: 267495 Cov.: 66 AF XY: 0.596 AC XY: 433137 AN XY: 727098

African (AFR) AF: 0.413 AC: 13816 AN: 33480

American (AMR) AF: 0.484 AC: 21654 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 15342 AN: 26130

East Asian (EAS) AF: 0.391 AC: 15504 AN: 39700

South Asian (SAS) AF: 0.420 AC: 36179 AN: 86232

European-Finnish (FIN) AF: 0.602 AC: 32098 AN: 53362

Middle Eastern (MID) AF: 0.651 AC: 3752 AN: 5764

European-Non Finnish (NFE) AF: 0.632 AC: 703193 AN: 1111852

Other (OTH) AF: 0.586 AC: 35398 AN: 60388

GnomAD4 genome AF: 0.552 AC: 83966 AN: 152132 Hom.: 23978 Cov.: 33 AF XY: 0.549 AC XY: 40827 AN XY: 74398

African (AFR) AF: 0.423 AC: 17573 AN: 41504

American (AMR) AF: 0.554 AC: 8475 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1993 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2104 AN: 5148

South Asian (SAS) AF: 0.411 AC: 1983 AN: 4824

European-Finnish (FIN) AF: 0.616 AC: 6528 AN: 10606

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43228 AN: 67970

Other (OTH) AF: 0.583 AC: 1228 AN: 2108

Alfa AF: 0.610 Hom.: 20112

Bravo AF: 0.546

TwinsUK AF: 0.632 AC: 2344

ALSPAC AF: 0.635 AC: 2448

ESP6500AA AF: 0.458 AC: 1866

ESP6500EA AF: 0.633 AC: 5288

ExAC AF: 0.551 AC: 66566

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.95
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.2
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.086
Vest4		0.48
ClinPred		0.033	T
GERP RS		1.4
Mutation Taster		=93/7	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: rs7191351; hg19: chr16-81249954; COSMIC: COSV61412777;