11-62626052-ATTGGTCACT-A

Position:

• chr11-62626052-ATTGGTCACT-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_198334.3(GANAB):​c.2725+4_2725+12delAGTGACCAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GANAB NM_198334.3 splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.65

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]

GANAB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-62626052-ATTGGTCACT-A is Pathogenic according to our data. Variant chr11-62626052-ATTGGTCACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 492969.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-62626052-ATTGGTCACT-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GANAB	NM_198334.3	c.2725+4_2725+12delAGTGACCAA		splice_region_variant, intron_variant		ENST00000356638.8	NP_938148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GANAB	ENST00000356638.8	c.2725+4_2725+12delAGTGACCAA		splice_region_variant, intron_variant		1	NM_198334.3	ENSP00000349053.3

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:1

Revision: no assertion criteria provided

Submissions by phenotype

POLYCYSTIC KIDNEY DISEASE 3 WITH POLYCYSTIC LIVER DISEASE Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 21, 2018

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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: rs1590789370; hg19: chr11-62393524;