17-80102109-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000152.5(GAA):c.-33+219G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,654 control chromosomes in the GnomAD database, including 42,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42568 hom., cov: 32)
  • Exomes 𝑓: 0.80 (180 hom.)
• Consequence: GAA NM_000152.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.92

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 17-80102109-G-C is Benign according to our data. Variant chr17-80102109-G-C is described in ClinVar as [Benign]. Clinvar id is 1237434.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAA	NM_000152.5	c.-33+219G>C		intron_variant		ENST00000302262.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAA	ENST00000302262.8	c.-33+219G>C		intron_variant		1	NM_000152.5	P1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113274 AN: 151966 Hom.: 42524 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.802 AC: 457 AN: 570 Hom.: 180 Cov.: 0 AF XY: 0.804 AC XY: 344 AN XY: 428

Gnomad4 AFR exome AF: 0.929

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.900

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.821

GnomAD4 genome AF: 0.745 AC: 113367 AN: 152084 Hom.: 42568 Cov.: 32 AF XY: 0.743 AC XY: 55260 AN XY: 74348

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.723

Alfa AF: 0.749 Hom.: 4985

Bravo AF: 0.731

Asia WGS AF: 0.735 AC: 2560 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.28
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4889961; hg19: chr17-78075908;