11-62626327-CCCATTA-C

Position:

• chr11-62626327-CCCATTA-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_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
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• 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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) 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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

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: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886037848; hg19: chr11-62393799;