chr16-81139516-G-A

Position:

• chr16-81139516-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000525539.5(PKD1L2):​c.5614C>T​(p.Pro1872Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,409,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PKD1L2 ENST00000525539.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52

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]

PKD1L2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.52

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L2	NR_126532.3	n.5629C>T		non_coding_transcript_exon_variant	32/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L2	ENST00000525539.5	c.5614C>T	p.Pro1872Ser	missense_variant	32/43	1		ENSP00000434417.1
PKD1L2	ENST00000533478.5	c.3559C>T	p.Pro1187Ser	missense_variant	21/32	1		ENSP00000434644.1
PKD1L2	ENST00000530363.5	n.203+1781C>T		intron_variant		1
PKD1L2	ENST00000299598.11	n.5011C>T		non_coding_transcript_exon_variant	22/25	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000106 AC: 15 AN: 1409542 Hom.: 0 Cov.: 30 AF XY: 0.0000129 AC XY: 9 AN XY: 696224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000412

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.5614C>T (p.P1872S) alteration is located in exon 32 (coding exon 32) of the PKD1L2 gene. This alteration results from a C to T substitution at nucleotide position 5614, causing the proline (P) at amino acid position 1872 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.52
CADD	Benign	17
DANN	Pathogenic	1.0

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: rs1346460572; hg19: chr16-81173121;