chr11-62626327-CCCATTA-C

Variant names:

• chr11-62626327-CCCATTA-C
• rs886037848
• NM_198334.3:c.2624+2_2624+7delTAATGG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_198334.3(GANAB):​c.2624+2_2624+7delTAATGG variant causes a splice donor, splice region, 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_region, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.12
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• polycystic kidney disease 3 with or without polycystic liver disease

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 253131.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GANAB	NM_198334.3	MANE Select	c.2624+2_2624+7delTAATGG		splice_donor splice_region intron	N/A	NP_938148.1	Q14697-1
	GANAB	NM_198335.4		c.2690+2_2690+7delTAATGG		splice_donor splice_region intron	N/A	NP_938149.2	Q14697-2
	GANAB	NM_001278192.2		c.2348+2_2348+7delTAATGG		splice_donor splice_region intron	N/A	NP_001265121.1	E9PKU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GANAB	ENST00000356638.8	TSL:1 MANE Select	c.2624+2_2624+7delTAATGG		splice_donor splice_region intron	N/A	ENSP00000349053.3	Q14697-1
	GANAB	ENST00000346178.8	TSL:1	c.2690+2_2690+7delTAATGG		splice_donor splice_region intron	N/A	ENSP00000340466.4	Q14697-2
	GANAB	ENST00000540933.5	TSL:1	c.2333+2_2333+7delTAATGG		splice_donor splice_region intron	N/A	ENSP00000442962.1	F5H6X6

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

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)
1	-	-	POLYCYSTIC KIDNEY DISEASE 3 WITH POLYCYSTIC LIVER DISEASE (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1
Mutation Taster		=0/100	disease causing (ClinVar)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs886037848;

hg19: chr11-62393799;