rs2304843

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1551+49C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 1,612,730 control chromosomes in the GnomAD database, including 405,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene GAA is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.65 ( 33381 hom., cov: 32)

Exomes 𝑓: 0.71 ( 372167 hom. )

Consequence

GAA
NM_000152.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.37

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: G2P, ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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

new If you want to explore the variant's impact on the transcript NM_000152.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for GAA are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-80110889-C-A is Benign according to our data. Variant chr17-80110889-C-A is described in ClinVar as Benign. ClinVar VariationId is 255352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GAA	NM_000152.5	MANE Select	c.1551+49C>A	intron	N/A	NP_000143.2	P10253
GAA	NM_001079803.3		c.1551+49C>A	intron	N/A	NP_001073271.1	P10253
GAA	NM_001079804.3		c.1551+49C>A	intron	N/A	NP_001073272.1	P10253

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GAA	ENST00000302262.8	TSL:1 MANE Select	c.1551+49C>A	intron	N/A	ENSP00000305692.3	P10253
GAA	ENST00000390015.7	TSL:1	c.1551+49C>A	intron	N/A	ENSP00000374665.3	P10253
GAA	ENST00000933406.1		c.1566+49C>A	intron	N/A	ENSP00000603465.1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99382

AN:

151852

Hom.:

33367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.529

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.771

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.655

Gnomad FIN

AF:

0.775

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.664

GnomAD2 exomes

AF:

0.669

AC:

167863

AN:

250994

AF XY:

0.683

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.475

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.529

Gnomad FIN exome

AF:

0.764

Gnomad NFE exome

AF:

0.740

Gnomad OTH exome

AF:

0.721

GnomAD4 exome

AF:

0.711

AC:

1038667

AN:

1460758

Hom.:

372167

Cov.:

AF XY:

0.712

AC XY:

517372

AN XY:

726768

show subpopulations

African (AFR)

AF:

0.531

AC:

17782

AN:

33458

American (AMR)

AF:

0.489

AC:

21850

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

20439

AN:

26130

East Asian (EAS)

AF:

0.560

AC:

22223

AN:

39694

South Asian (SAS)

AF:

0.666

AC:

57445

AN:

86236

European-Finnish (FIN)

AF:

0.766

AC:

40810

AN:

53306

Middle Eastern (MID)

AF:

0.795

AC:

4584

AN:

5768

European-Non Finnish (NFE)

AF:

0.730

AC:

810779

AN:

1111110

Other (OTH)

AF:

0.708

AC:

42755

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

18950

37900

56849

75799

94749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19892

39784

59676

79568

99460

<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:

0.654

AC:

99426

AN:

151972

Hom.:

33381

Cov.:

AF XY:

0.652

AC XY:

48433

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.529

AC:

21920

AN:

41454

American (AMR)

AF:

0.556

AC:

8496

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.771

AC:

2673

AN:

3468

East Asian (EAS)

AF:

0.538

AC:

2763

AN:

5136

South Asian (SAS)

AF:

0.654

AC:

3151

AN:

4820

European-Finnish (FIN)

AF:

0.775

AC:

8199

AN:

10576

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.736

AC:

49983

AN:

67932

Other (OTH)

AF:

0.663

AC:

1401

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1683

3365

5048

6730

8413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.693

Hom.:

9785

Bravo

AF:

0.635

Asia WGS

AF:

0.577

AC:

2012

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Glycogen storage disease, type II (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.6

(source)

DANN

Benign

0.84

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over