17-80117129-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.215

Publications

15 publications found

Variant links:

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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, G2P
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

GAA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAA	NM_000152.5 link	c.2331+20G>A		intron_variant	Intron 16 of 19	ENST00000302262.8	NP_000143.2	P10253

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAA	ENST00000302262.8 link	c.2331+20G>A		intron_variant	Intron 16 of 19	1	NM_000152.5	ENSP00000305692.3		P10253

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

120997

AN:

152006

Hom.:

49110

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.754

AC XY:

546841

AN XY:

725140

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13418

26836

40253

53671

67089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20198

40396

60594

80792

100990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.796

AC:

121097

AN:

152124

Hom.:

49159

Cov.:

AF XY:

0.792

AC XY:

58914

AN XY:

74382

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1215

2430

3644

4859

6074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

866

1732

2598

3464

4330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.782

Hom.:

8684

Bravo

AF:

0.788

Asia WGS

AF:

0.745

AC:

2594

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 12, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Glycogen storage disease, type II

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.77

(source)

DANN

Benign

0.34

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over