17-80110708-G-C

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.1438-19G>C 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 1,610,108 control chromosomes in the GnomAD database, including 405,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.66 ( 33489 hom., cov: 33)

Exomes 𝑓: 0.71 ( 372161 hom. )

Consequence

GAA
NM_000152.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.190

Publications

18 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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-80110708-G-C is Benign according to our data. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80110708-G-C is described in CliVar as Benign. Clinvar id is 92464.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAA	NM_000152.5 link	c.1438-19G>C		intron_variant	Intron 9 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.1438-19G>C		intron_variant	Intron 9 of 19	1	NM_000152.5	ENSP00000305692.3		P10253

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99623

AN:

151992

Hom.:

33476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.649

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.775

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.667

GnomAD2 exomes

AF:

0.670

AC:

167242

AN:

249778

AF XY:

0.684

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.475

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.528

Gnomad FIN exome

AF:

0.764

Gnomad NFE exome

AF:

0.740

Gnomad OTH exome

AF:

0.721

GnomAD4 exome

AF:

0.712

AC:

1037728

AN:

1457998

Hom.:

372161

Cov.:

AF XY:

0.713

AC XY:

517085

AN XY:

725436

show subpopulations

African (AFR)

AF:

0.534

AC:

17822

AN:

33394

American (AMR)

AF:

0.489

AC:

21843

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

20423

AN:

26104

East Asian (EAS)

AF:

0.560

AC:

22220

AN:

39682

South Asian (SAS)

AF:

0.673

AC:

58036

AN:

86176

European-Finnish (FIN)

AF:

0.766

AC:

40678

AN:

53120

Middle Eastern (MID)

AF:

0.794

AC:

4227

AN:

5326

European-Non Finnish (NFE)

AF:

0.730

AC:

809735

AN:

1109268

Other (OTH)

AF:

0.709

AC:

42744

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

17081

34162

51242

68323

85404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19848

39696

59544

79392

99240

<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:

0.655

AC:

99667

AN:

152110

Hom.:

33489

Cov.:

AF XY:

0.653

AC XY:

48561

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.532

AC:

22048

AN:

41480

American (AMR)

AF:

0.556

AC:

8510

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.770

AC:

2675

AN:

3472

East Asian (EAS)

AF:

0.539

AC:

2778

AN:

5158

South Asian (SAS)

AF:

0.660

AC:

3184

AN:

4824

European-Finnish (FIN)

AF:

0.775

AC:

8226

AN:

10610

Middle Eastern (MID)

AF:

0.850

AC:

250

AN:

294

European-Non Finnish (NFE)

AF:

0.736

AC:

49997

AN:

67952

Other (OTH)

AF:

0.666

AC:

1407

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1689

3377

5066

6754

8443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.711

Hom.:

7129

Bravo

AF:

0.636

Asia WGS

AF:

0.587

AC:

2046

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

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 04, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glycogen storage disease, type II

Benign:3

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

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

-0.91

CADD

Benign

4.2

(source)

DANN

Benign

0.35

PhyloP100

-0.19

BranchPoint Hunter

3.0

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