rs12596941

chr16-81174910-G-Achr16-81174910-G-T

Variant summary

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

The ENST00000531391.5(PKD1L2):c.533C>T(p.Ala178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,598,096 control chromosomes in the GnomAD database, including 49,841 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 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 0.19 (3455 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46386 hom.)
• Consequence: PKD1L2 ENST00000531391.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021180212).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L2	NR_126532.3	n.2603C>T		non_coding_transcript_exon_variant	16/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L2	ENST00000525539.5	c.2588C>T	p.Ala863Val	missense_variant	16/43	1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28919 AN: 151966 Hom.: 3456 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.247 AC: 59081 AN: 239346 Hom.: 8068 AF XY: 0.248 AC XY: 32122 AN XY: 129768

Gnomad AFR exome AF: 0.0453

Gnomad AMR exome AF: 0.294

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.316

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.247 AC: 357526 AN: 1446012 Hom.: 46386 Cov.: 33 AF XY: 0.248 AC XY: 177895 AN XY: 717510

Gnomad4 AFR exome AF: 0.0409

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.315

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.190 AC: 28917 AN: 152084 Hom.: 3455 Cov.: 32 AF XY: 0.196 AC XY: 14549 AN XY: 74348

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.178

Alfa AF: 0.214 Hom.: 7829

Bravo AF: 0.179

TwinsUK AF: 0.250 AC: 927

ALSPAC AF: 0.246 AC: 947

ESP6500AA AF: 0.0496 AC: 202

ESP6500EA AF: 0.224 AC: 1882

ExAC AF: 0.241 AC: 29093

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	12
Dann	Benign	0.84
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.72	T;T;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.036
Polyphen		0.23, 0.078	.;B;B
Vest4		0.14
MPC		.;.;6.49843439168E-4
ClinPred		0.00099	T
GERP RS		0.36

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: rs12596941; hg19: chr16-81208515; COSMIC: COSV55158254;