16-81137521-C-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The ENST00000525539.5(PKD1L2):c.5635G>C(p.Ala1879Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,040 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
PKD1L2
ENST00000525539.5 missense
ENST00000525539.5 missense
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 7.15
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
BayesDel_noAF computational evidence supports a deleterious effect, 0.53
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1L2 | NR_126532.3 | n.5650G>C | non_coding_transcript_exon_variant | 33/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1L2 | ENST00000525539.5 | c.5635G>C | p.Ala1879Pro | missense_variant | 33/43 | 1 | |||
PKD1L2 | ENST00000533478.5 | c.3580G>C | p.Ala1194Pro | missense_variant | 22/32 | 1 | |||
PKD1L2 | ENST00000530363.5 | n.216G>C | non_coding_transcript_exon_variant | 2/6 | 1 | ||||
PKD1L2 | ENST00000299598.11 | n.5032G>C | non_coding_transcript_exon_variant | 23/25 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152040Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 31
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74262
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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 | Jan 10, 2023 | The c.5635G>C (p.A1879P) alteration is located in exon 33 (coding exon 33) of the PKD1L2 gene. This alteration results from a G to C substitution at nucleotide position 5635, causing the alanine (A) at amino acid position 1879 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
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BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at