rs8044334

Variant names:

• chr16-81215330-T-G
• rs8044334
• ENST00000525539.5:c.464-136A>C

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.464-136A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 795,264 control chromosomes in the GnomAD database, including 52,605 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (12068 hom., cov: 30)
  • Exomes 𝑓: 0.35 (40537 hom.)
• Consequence: PKD1L2 ENST00000525539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 11 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.488-136A>C		intron_variant	Intron 2 of 42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.464-136A>C		intron_variant	Intron 2 of 42	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58678 AN: 151528 Hom.: 12055 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.348 AC: 223889 AN: 643618 Hom.: 40537 AF XY: 0.345 AC XY: 112308 AN XY: 325186

African (AFR) AF: 0.527 AC: 8062 AN: 15286

American (AMR) AF: 0.317 AC: 4963 AN: 15660

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 3275 AN: 13816

East Asian (EAS) AF: 0.393 AC: 11693 AN: 29750

South Asian (SAS) AF: 0.308 AC: 12017 AN: 39016

European-Finnish (FIN) AF: 0.353 AC: 10143 AN: 28740

Middle Eastern (MID) AF: 0.258 AC: 930 AN: 3602

European-Non Finnish (NFE) AF: 0.347 AC: 161710 AN: 466610

Other (OTH) AF: 0.356 AC: 11096 AN: 31138

GnomAD4 genome AF: 0.387 AC: 58754 AN: 151646 Hom.: 12068 Cov.: 30 AF XY: 0.386 AC XY: 28602 AN XY: 74110

African (AFR) AF: 0.529 AC: 21859 AN: 41324

American (AMR) AF: 0.327 AC: 4989 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3468

East Asian (EAS) AF: 0.405 AC: 2078 AN: 5128

South Asian (SAS) AF: 0.272 AC: 1307 AN: 4800

European-Finnish (FIN) AF: 0.372 AC: 3919 AN: 10528

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22669 AN: 67840

Other (OTH) AF: 0.347 AC: 731 AN: 2106

Alfa AF: 0.346 Hom.: 39064

Bravo AF: 0.394

Asia WGS AF: 0.411 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.32
PhyloP100		0.13
Mutation Taster		=100/0	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: rs8044334; hg19: chr16-81248935;