Variant rs2304837 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000152.5(GAA):c.1888+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 1,598,582 control chromosomes in the GnomAD database, including 2,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 308 hom., cov: 33)

Exomes 𝑓: 0.046 ( 2665 hom. )

Consequence

GAA
NM_000152.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.474

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 links:

GAA (HGNC:):

GAA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-80112732-G-A is Benign according to our data. Variant chr17-80112732-G-A is described in ClinVar as [Benign]. Clinvar id is 255357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80112732-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAA	NM_000152.5 linkuse as main transcript	c.1888+21G>A		intron_variant		ENST00000302262.8	NP_000143.2	P10253

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAA	ENST00000302262.8 linkuse as main transcript	c.1888+21G>A		intron_variant		1	NM_000152.5	ENSP00000305692.3		P10253

Frequencies

GnomAD3 genomes

AF:

0.0437

AC:

6643

AN:

152178

Hom.:

305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0391

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.0687

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0395

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0577

AC:

12313

AN:

213296

Hom.:

682

AF XY:

0.0577

AC XY:

6743

AN XY:

116894

show subpopulations

Gnomad AFR exome

AF:

0.0199

Gnomad AMR exome

AF:

0.0268

Gnomad ASJ exome

AF:

0.0415

Gnomad EAS exome

AF:

0.239

Gnomad SAS exome

AF:

0.0644

Gnomad FIN exome

AF:

0.0651

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0591

GnomAD4 exome

AF:

0.0458

AC:

66311

AN:

1446286

Hom.:

2665

Cov.:

AF XY:

0.0465

AC XY:

33394

AN XY:

718268

show subpopulations

Gnomad4 AFR exome

AF:

0.0196

Gnomad4 AMR exome

AF:

0.0276

Gnomad4 ASJ exome

AF:

0.0427

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.0618

Gnomad4 FIN exome

AF:

0.0679

Gnomad4 NFE exome

AF:

0.0375

Gnomad4 OTH exome

AF:

0.0525

GnomAD4 genome

AF:

0.0437

AC:

6657

AN:

152296

Hom.:

308

Cov.:

AF XY:

0.0455

AC XY:

3386

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0203

Gnomad4 AMR

AF:

0.0389

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.0689

Gnomad4 FIN

AF:

0.0652

Gnomad4 NFE

AF:

0.0395

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0286

Hom.:

Bravo

AF:

0.0399

Asia WGS

AF:

0.155

AC:

541

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -

Glycogen storage disease, type II

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Counsyl	Dec 08, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.3

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over