chr16-81147409-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000525539.5(PKD1L2):c.5077T>G(p.Leu1693Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
PKD1L2
ENST00000525539.5 missense
ENST00000525539.5 missense
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.11
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.11).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1L2 | NR_126532.3 | n.5092T>G | non_coding_transcript_exon_variant | 30/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1L2 | ENST00000525539.5 | c.5077T>G | p.Leu1693Val | missense_variant | 30/43 | 1 | |||
PKD1L2 | ENST00000533478.5 | c.3022T>G | p.Leu1008Val | missense_variant | 19/32 | 1 | |||
PKD1L2 | ENST00000299598.11 | n.4474T>G | non_coding_transcript_exon_variant | 20/25 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249264Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135222
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461674Hom.: 0 Cov.: 38 AF XY: 0.0000468 AC XY: 34AN XY: 727110
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2023 | The c.5077T>G (p.L1693V) alteration is located in exon 30 (coding exon 30) of the PKD1L2 gene. This alteration results from a T to G substitution at nucleotide position 5077, causing the leucine (L) at amino acid position 1693 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at