rs12596941

Variant names:

• chr16-81174910-G-A
• rs12596941
• ENST00000525539.5:c.2588C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-81174910-G-A
• chr16-81174910-G-T

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.2588C>T​(p.Ala863Val) 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. 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 0.19 (3455 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46386 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 24 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=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 rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.2603C>T		non_coding_transcript_exon_variant	Exon 16 of 43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.2588C>T	p.Ala863Val	missense_variant	Exon 16 of 43	1		ENSP00000434417.1

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

GnomAD2 exomes AF: 0.247 AC: 59081 AN: 239346 AF XY: 0.248

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 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

African (AFR) AF: 0.0409 AC: 1351 AN: 33048

American (AMR) AF: 0.281 AC: 12144 AN: 43268

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3780 AN: 25206

East Asian (EAS) AF: 0.340 AC: 13414 AN: 39470

South Asian (SAS) AF: 0.315 AC: 26570 AN: 84426

European-Finnish (FIN) AF: 0.287 AC: 15122 AN: 52690

Middle Eastern (MID) AF: 0.136 AC: 771 AN: 5688

European-Non Finnish (NFE) AF: 0.246 AC: 270696 AN: 1102596

Other (OTH) AF: 0.229 AC: 13678 AN: 59620

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

African (AFR) AF: 0.0485 AC: 2013 AN: 41514

American (AMR) AF: 0.227 AC: 3471 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1719 AN: 5166

South Asian (SAS) AF: 0.319 AC: 1537 AN: 4822

European-Finnish (FIN) AF: 0.284 AC: 2994 AN: 10558

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16031 AN: 67974

Other (OTH) AF: 0.178 AC: 375 AN: 2106

Alfa AF: 0.210 Hom.: 12521

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
AlphaMissense	Benign	0.11
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
PhyloP100		0.18
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
Mutation Taster		=95/5	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: rs12596941; hg19: chr16-81208515; COSMIC: COSV55158254;