16-81218241-A-T

Variant names:

• chr16-81218241-A-T
• rs7199144
• ENST00000525539.5:c.301+1829T>A

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.301+1829T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,002 control chromosomes in the GnomAD database, including 10,491 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 0.36 (10491 hom., cov: 33)
• Consequence: PKD1L2 ENST00000525539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 4 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.325+1829T>A		intron_variant	Intron 1 of 42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.301+1829T>A		intron_variant	Intron 1 of 42	1		ENSP00000434417.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55413 AN: 151884 Hom.: 10484 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55465 AN: 152002 Hom.: 10491 Cov.: 33 AF XY: 0.365 AC XY: 27088 AN XY: 74312

African (AFR) AF: 0.457 AC: 18903 AN: 41408

American (AMR) AF: 0.335 AC: 5109 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2038 AN: 5170

South Asian (SAS) AF: 0.267 AC: 1287 AN: 4820

European-Finnish (FIN) AF: 0.372 AC: 3928 AN: 10568

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22338 AN: 67986

Other (OTH) AF: 0.327 AC: 689 AN: 2106

Alfa AF: 0.234 Hom.: 542

Bravo AF: 0.371

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.44
PhyloP100		-1.8
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: rs7199144; hg19: chr16-81251846;