rs752024467
Variant summary
Our verdict is Pathogenic. Variant got 22 ACMG points: 22P and 0B. PVS1PM2PP3_StrongPP5_Very_Strong
The NM_000297.4(PKD2):c.1548+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000297.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 22 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD2 | NM_000297.4 | c.1548+1G>A | splice_donor_variant | ENST00000237596.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD2 | ENST00000237596.7 | c.1548+1G>A | splice_donor_variant | 1 | NM_000297.4 | P1 | |||
PKD2 | ENST00000508588.5 | c.-199+3414G>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251168Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135788
GnomAD4 exome AF: 7.06e-7 AC: 1AN: 1415694Hom.: 0 Cov.: 25 AF XY: 0.00000141 AC XY: 1AN XY: 707294
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal dominant polycystic kidney disease Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 04, 2021 | ClinVar contains an entry for this variant (Variation ID: 562283). Disruption of this splice site has been observed in individual(s) with autosomal dominant polycystic kidney disease (PMID: 31740684). This variant is present in population databases (rs752024467, ExAC 0.006%). This sequence change affects a donor splice site in intron 6 of the PKD2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PKD2 are known to be pathogenic (PMID: 17582161, 22863349). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Polycystic kidney disease 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 10, 2021 | - - |
not provided Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at