rs1800317

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.*3G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 1,613,106 control chromosomes in the GnomAD database, including 2,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 548 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1841 hom. )

Consequence

GAA
NM_000152.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -7.35

Publications

9 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=-0.98).

BP6

Variant 17-80119334-G-A is Benign according to our data. Variant chr17-80119334-G-A is described in ClinVar as Benign. ClinVar VariationId is 92459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAA	NM_000152.5 link	c.*3G>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000302262.8	NP_000143.2	P10253

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAA	ENST00000302262.8 link	c.*3G>A		3_prime_UTR_variant	Exon 20 of 20	1	NM_000152.5	ENSP00000305692.3		P10253

Frequencies

GnomAD3 genomes

AF:

0.0596

AC:

9068

AN:

152064

Hom.:

547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.0902

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0333

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0354

GnomAD2 exomes

AF:

0.0490

AC:

12312

AN:

251086

AF XY:

0.0502

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0374

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.0897

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.0317

GnomAD4 exome

AF:

0.0290

AC:

42332

AN:

1460924

Hom.:

1841

Cov.:

AF XY:

0.0315

AC XY:

22891

AN XY:

726830

show subpopulations

African (AFR)

AF:

0.147

AC:

4909

AN:

33438

American (AMR)

AF:

0.0349

AC:

1560

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0175

AC:

456

AN:

26124

East Asian (EAS)

AF:

0.102

AC:

4044

AN:

39690

South Asian (SAS)

AF:

0.136

AC:

11754

AN:

86228

European-Finnish (FIN)

AF:

0.0317

AC:

1695

AN:

53400

Middle Eastern (MID)

AF:

0.0201

AC:

116

AN:

5766

European-Non Finnish (NFE)

AF:

0.0140

AC:

15575

AN:

1111194

Other (OTH)

AF:

0.0368

AC:

2223

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2299

4597

6896

9194

11493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

822

1644

2466

3288

4110

<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:

0.0597

AC:

9086

AN:

152182

Hom.:

548

Cov.:

AF XY:

0.0614

AC XY:

4570

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.146

AC:

6044

AN:

41482

American (AMR)

AF:

0.0279

AC:

427

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0158

AC:

AN:

3472

East Asian (EAS)

AF:

0.0900

AC:

466

AN:

5176

South Asian (SAS)

AF:

0.151

AC:

728

AN:

4812

European-Finnish (FIN)

AF:

0.0333

AC:

354

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0137

AC:

933

AN:

68008

Other (OTH)

AF:

0.0360

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

391

782

1174

1565

1956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0258

Hom.:

Bravo

AF:

0.0600

Asia WGS

AF:

0.137

AC:

476

AN:

3478

EpiCase

AF:

0.0111

EpiControl

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 17, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Glycogen storage disease, type II

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 01, 2017

Phosphorus, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 22, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 13, 2013

Eurofins Ntd Llc (ga)

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

-0.98

CADD

Benign

0.85

(source)

DANN

Benign

0.50

PhyloP100

-7.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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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