chr2-63152913-C-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PM2PP3_Strong
The NM_015910.7(WDPCP):c.2190+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,140 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 Uncertain significance (★★).
Frequency
Consequence
NM_015910.7 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WDPCP | NM_015910.7 | c.2190+1G>A | splice_donor_variant | ENST00000272321.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WDPCP | ENST00000272321.12 | c.2190+1G>A | splice_donor_variant | 1 | NM_015910.7 | P1 | |||
ENST00000657946.1 | n.131-7205C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459060Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726068
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74276
ClinVar
Submissions by phenotype
Heart defect - tongue hamartoma - polysyndactyly syndrome;C3150127:Bardet-Biedl syndrome 15 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 20, 2022 | - - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 31, 2022 | ClinVar contains an entry for this variant (Variation ID: 1448082). This variant has not been reported in the literature in individuals affected with WDPCP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 17 of the WDPCP gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at