rs2304831

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.2331+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,608,916 control chromosomes in the GnomAD database, including 17,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1835 hom., cov: 33)

Exomes 𝑓: 0.13 ( 15233 hom. )

Consequence

GAA
NM_000152.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.32

Publications

6 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=-1.02).

BP6

Variant 17-80117133-T-C is Benign according to our data. Variant chr17-80117133-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAA	NM_000152.5 link	c.2331+24T>C		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+24T>C		intron_variant	Intron 16 of 19	1	NM_000152.5	ENSP00000305692.3		P10253

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21741

AN:

152082

Hom.:

1830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.0960

Gnomad ASJ

AF:

0.0935

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.149

AC:

36519

AN:

244470

AF XY:

0.152

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.0833

Gnomad ASJ exome

AF:

0.0970

Gnomad EAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.131

AC:

191528

AN:

1456716

Hom.:

15233

Cov.:

AF XY:

0.134

AC XY:

97123

AN XY:

724778

show subpopulations

African (AFR)

AF:

0.168

AC:

5636

AN:

33450

American (AMR)

AF:

0.0841

AC:

3757

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2643

AN:

26126

East Asian (EAS)

AF:

0.392

AC:

15554

AN:

39656

South Asian (SAS)

AF:

0.233

AC:

20048

AN:

86180

European-Finnish (FIN)

AF:

0.155

AC:

7685

AN:

49654

Middle Eastern (MID)

AF:

0.0610

AC:

345

AN:

5660

European-Non Finnish (NFE)

AF:

0.115

AC:

127593

AN:

1111038

Other (OTH)

AF:

0.137

AC:

8267

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

7662

15324

22985

30647

38309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4858

9716

14574

19432

24290

<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:

0.143

AC:

21781

AN:

152200

Hom.:

1835

Cov.:

AF XY:

0.145

AC XY:

10783

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.170

AC:

7079

AN:

41526

American (AMR)

AF:

0.0960

AC:

1468

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0935

AC:

324

AN:

3466

East Asian (EAS)

AF:

0.351

AC:

1817

AN:

5170

South Asian (SAS)

AF:

0.252

AC:

1212

AN:

4818

European-Finnish (FIN)

AF:

0.152

AC:

1612

AN:

10620

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7823

AN:

67984

Other (OTH)

AF:

0.117

AC:

247

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

962

1924

2887

3849

4811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.123

Hom.:

276

Bravo

AF:

0.138

Asia WGS

AF:

0.327

AC:

1137

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glycogen storage disease, type II

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.17

(source)

DANN

Benign

0.36

PhyloP100

-3.3

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