Variant rs2304843 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.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 (★★).

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

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:

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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=-0.79).

BP6

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

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/exons	MANE	UniProt
GAA	NM_000152.5 linkuse as main transcript	c.1551+49C>A		intron_variant		ENST00000302262.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAA	ENST00000302262.8 linkuse as main transcript	c.1551+49C>A		intron_variant		1	NM_000152.5	P1

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

GnomAD3 exomes

AF:

0.669

AC:

167863

AN:

250994

Hom.:

57800

AF XY:

0.683

AC XY:

92699

AN XY:

135758

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 SAS exome

AF:

0.667

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

Gnomad4 AFR exome

AF:

0.531

Gnomad4 AMR exome

AF:

0.489

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.666

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.730

Gnomad4 OTH exome

AF:

0.708

GnomAD4 genome

AF:

0.654

AC:

99426

AN:

151972

Hom.:

33381

Cov.:

AF XY:

0.652

AC XY:

48433

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.529

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.771

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.654

Gnomad4 FIN

AF:

0.775

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.663

Alfa

AF:

0.682

Hom.:

4422

Bravo

AF:

0.635

Asia WGS

AF:

0.577

AC:

2012

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Glycogen storage disease, type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.6

DANN

Benign

0.84

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

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