rs3071247

Positions:

• chr17-80107727-A-AGCACCGG
• chr17-80107727-A-AGCAGCAG
• chr17-80107727-A-AGCAGCGG
• chr17-80107727-A-AGCAGCGGGCGGCGG
• chr17-80107727-A-AGCAGCGGGCGGCGGGCAGCGG
• chr17-80107727-A-AGCAGCGGGCGGCGGGCGGCGG
• chr17-80107727-A-AGCAGCGGGTGGCGG
• chr17-80107727-A-AGCAGTGG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000302262.8(GAA):​c.858+7_858+8insACCGGGC variant causes a splice donor 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: GAA ENST00000302262.8 splice_donor_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.160

Genes affected

GAA (HGNC:4065): (alpha glucosidase) This gene encodes lysosomal alpha-glucosidase, which is essential for the degradation of glycogen to glucose in lysosomes. The encoded preproprotein is proteolytically processed to generate multiple intermediate forms and the mature form of the enzyme. Defects in this gene are the cause of glycogen storage disease II, also known as Pompe's disease, which is an autosomal recessive disorder with a broad clinical spectrum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-80107727-A-AGCACCGG is Benign according to our data. Variant chr17-80107727-A-AGCACCGG is described in ClinVar as [Likely_benign]. Clinvar id is 1103967.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAA	NM_000152.5	c.858+7_858+8insACCGGGC		splice_donor_region_variant, intron_variant		ENST00000302262.8	NP_000143.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAA	ENST00000302262.8	c.858+7_858+8insACCGGGC		splice_donor_region_variant, intron_variant		1	NM_000152.5	ENSP00000305692	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Glycogen storage disease, type II Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78081526;