16-81122917-T-C

Position:

• chr16-81122917-T-C

Variant summary

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

The ENST00000525539.5(PKD1L2):​c.6483+734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,114 control chromosomes in the GnomAD database, including 17,380 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 0.46 (17377 hom., cov: 33)
  • Exomes 𝑓: 0.58 (3 hom.)
• Consequence: PKD1L2 ENST00000525539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.6498+734A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.6483+734A>G		intron_variant		1		ENSP00000434417
PKD1L2	ENST00000533478.5	c.4428+734A>G		intron_variant		1		ENSP00000434644
PKD1L2	ENST00000534142.5	n.872+734A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69381 AN: 151984 Hom.: 17365 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.583 AC: 7 AN: 12 Hom.: 3 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.456 AC: 69401 AN: 152102 Hom.: 17377 Cov.: 33 AF XY: 0.457 AC XY: 33956 AN XY: 74320

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.482

Alfa AF: 0.522 Hom.: 21236

Bravo AF: 0.445

Asia WGS AF: 0.431 AC: 1502 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	7.9
DANN	Benign	0.60

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: rs4889240; hg19: chr16-81156522;