rs7198127

Positions:

• chr16-81167024-G-A
• chr16-81167024-G-C

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.3093+895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,984 control chromosomes in the GnomAD database, including 33,271 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 0.65 (33271 hom., cov: 32)
• Consequence: PKD1L2 ENST00000525539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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 (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.3108+895C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.3093+895C>T		intron_variant		1		ENSP00000434417
PKD1L2	ENST00000533478.5	c.1038+895C>T		intron_variant		1		ENSP00000434644
PKD1L2	ENST00000299598.11	n.1422+895C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99273 AN: 151866 Hom.: 33249 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.654 AC: 99342 AN: 151984 Hom.: 33271 Cov.: 32 AF XY: 0.660 AC XY: 49083 AN XY: 74320

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.672

Alfa AF: 0.687 Hom.: 74122

Bravo AF: 0.650

Asia WGS AF: 0.731 AC: 2543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.62
DANN	Benign	0.73

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: rs7198127; hg19: chr16-81200629;