16-81122917-T-C

Variant names:

• chr16-81122917-T-C
• rs4889240
• ENST00000525539.5:c.6483+734A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.6498+734A>G		intron_variant	Intron 37 of 42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.6483+734A>G		intron_variant	Intron 37 of 42	1		ENSP00000434417.1
PKD1L2	ENST00000533478.5	c.4428+734A>G		intron_variant	Intron 26 of 31	1		ENSP00000434644.1
PKD1L2	ENST00000534142.5	n.872+734A>G		intron_variant	Intron 5 of 10	2
PKD1L2	ENST00000530363.5	n.*101A>G		downstream_gene_variant		1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.236 AC: 9795 AN: 41482

American (AMR) AF: 0.514 AC: 7849 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2010 AN: 5176

South Asian (SAS) AF: 0.516 AC: 2484 AN: 4816

European-Finnish (FIN) AF: 0.523 AC: 5529 AN: 10580

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.562 AC: 38221 AN: 67994

Other (OTH) AF: 0.482 AC: 1018 AN: 2114

Alfa AF: 0.495 Hom.: 28252

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
PhyloP100		0.88

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: rs4889240; hg19: chr16-81156522;