rs2304842

Positions:

• chr17-80111068-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000152.5(GAA):​c.1636+43G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,580,600 control chromosomes in the GnomAD database, including 2,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (547 hom., cov: 33)
  • Exomes 𝑓: 0.029 (1831 hom.)
• Consequence: GAA NM_000152.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.524

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-80111068-G-T is Benign according to our data. Variant chr17-80111068-G-T is described in ClinVar as [Benign]. Clinvar id is 255355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAA	NM_000152.5	c.1636+43G>T		intron_variant		ENST00000302262.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAA	ENST00000302262.8	c.1636+43G>T		intron_variant		1	NM_000152.5	P1

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8974 AN: 152072 Hom.: 546 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.0496 AC: 11687 AN: 235428 Hom.: 600 AF XY: 0.0509 AC XY: 6516 AN XY: 127924

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0376

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0919

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.0334

Gnomad NFE exome AF: 0.0148

Gnomad OTH exome AF: 0.0315

GnomAD4 exome AF: 0.0293 AC: 41811 AN: 1428410 Hom.: 1831 Cov.: 27 AF XY: 0.0318 AC XY: 22603 AN XY: 711906

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0349

Gnomad4 ASJ exome AF: 0.0197

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0315

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.0358

GnomAD4 genome AF: 0.0591 AC: 8992 AN: 152190 Hom.: 547 Cov.: 33 AF XY: 0.0605 AC XY: 4505 AN XY: 74408

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.0943

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0329

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0313 Hom.: 38

Bravo AF: 0.0594

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Glycogen storage disease, type II Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.36

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: rs2304842; hg19: chr17-78084867;