rs2304832

Variant names:

• chr17-80117129-G-A
• rs2304832
• NM_000152.5:c.2331+20G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80117129-G-A
• chr17-80117129-G-T
• chr17-80117129-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000152.5(GAA):​c.2331+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,609,616 control chromosomes in the GnomAD database, including 463,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49159 hom., cov: 33)
  • Exomes 𝑓: 0.75 (414378 hom.)
• Consequence: GAA NM_000152.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.215
• Publications: 15 publications found

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]

GAA Gene-Disease associations (from GenCC):

• glycogen storage disease II

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
• glycogen storage disease due to acid maltase deficiency, infantile onset

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• glycogen storage disease due to acid maltase deficiency, late-onset

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 17-80117129-G-A is Benign according to our data. Variant chr17-80117129-G-A is described in ClinVar as Benign. ClinVar VariationId is 92474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000152.5. 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
	GAA	NM_000152.5	MANE Select	c.2331+20G>A		intron	N/A	NP_000143.2	P10253
	GAA	NM_001079803.3		c.2331+20G>A		intron	N/A	NP_001073271.1	P10253
	GAA	NM_001079804.3		c.2331+20G>A		intron	N/A	NP_001073272.1	P10253

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAA	ENST00000302262.8	TSL:1 MANE Select	c.2331+20G>A		intron	N/A	ENSP00000305692.3	P10253
	GAA	ENST00000390015.7	TSL:1	c.2331+20G>A		intron	N/A	ENSP00000374665.3	P10253
	GAA	ENST00000933406.1		c.2346+20G>A		intron	N/A	ENSP00000603465.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120997 AN: 152006 Hom.: 49110 Cov.: 33

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.767

GnomAD2 exomes AF: 0.742 AC: 181849 AN: 245184 AF XY: 0.751

Gnomad AFR exome AF: 0.956

Gnomad AMR exome AF: 0.529

Gnomad ASJ exome AF: 0.824

Gnomad EAS exome AF: 0.619

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.758

Gnomad OTH exome AF: 0.767

GnomAD4 exome AF: 0.752 AC: 1095614 AN: 1457492 Hom.: 414378 Cov.: 40 AF XY: 0.754 AC XY: 546841 AN XY: 725140

African (AFR) AF: 0.961 AC: 32176 AN: 33474

American (AMR) AF: 0.543 AC: 24235 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 21515 AN: 26130

East Asian (EAS) AF: 0.674 AC: 26719 AN: 39666

South Asian (SAS) AF: 0.808 AC: 69684 AN: 86208

European-Finnish (FIN) AF: 0.799 AC: 40158 AN: 50280

Middle Eastern (MID) AF: 0.853 AC: 4856 AN: 5696

European-Non Finnish (NFE) AF: 0.747 AC: 829910 AN: 1111106

Other (OTH) AF: 0.769 AC: 46361 AN: 60308

GnomAD4 genome AF: 0.796 AC: 121097 AN: 152124 Hom.: 49159 Cov.: 33 AF XY: 0.792 AC XY: 58914 AN XY: 74382

African (AFR) AF: 0.948 AC: 39366 AN: 41522

American (AMR) AF: 0.623 AC: 9532 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2833 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3252 AN: 5156

South Asian (SAS) AF: 0.810 AC: 3900 AN: 4814

European-Finnish (FIN) AF: 0.809 AC: 8577 AN: 10600

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51166 AN: 67950

Other (OTH) AF: 0.767 AC: 1618 AN: 2110

Alfa AF: 0.782 Hom.: 8684

Bravo AF: 0.788

Asia WGS AF: 0.745 AC: 2594 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Glycogen storage disease, type II (3)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.77
DANN	Benign	0.34
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2304832; hg19: chr17-78090928;