rs886037848
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_198334.3(GANAB):c.2624+2_2624+7del variant causes a splice donor, splice donor 5th base, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
GANAB
NM_198334.3 splice_donor, splice_donor_5th_base, intron
NM_198334.3 splice_donor, splice_donor_5th_base, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.12
Genes affected
GANAB (HGNC:4138): (glucosidase II alpha subunit) This gene encodes the alpha subunit of glucosidase II and a member of the glycosyl hydrolase 31 family of proteins. The heterodimeric enzyme glucosidase II plays a role in protein folding and quality control by cleaving glucose residues from immature glycoproteins in the endoplasmic reticulum. Expression of the encoded protein is elevated in lung tumor tissue and in response to UV irradiation. Mutations in this gene cause autosomal-dominant polycystic kidney and liver disease. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-62626327-CCCATTA-C is Pathogenic according to our data. Variant chr11-62626327-CCCATTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 253131.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-62626327-CCCATTA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GANAB | NM_198334.3 | c.2624+2_2624+7del | splice_donor_variant, splice_donor_5th_base_variant, intron_variant | ENST00000356638.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GANAB | ENST00000356638.8 | c.2624+2_2624+7del | splice_donor_variant, splice_donor_5th_base_variant, intron_variant | 1 | NM_198334.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
POLYCYSTIC KIDNEY DISEASE 3 WITH POLYCYSTIC LIVER DISEASE Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 22, 2018 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 06, 2023 | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27259053) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at