Variant rs2304831 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.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

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=-1.02).

BP6

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

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/exons	MANE	UniProt
GAA	NM_000152.5 linkuse as main transcript	c.2331+24T>C		intron_variant		ENST00000302262.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAA	ENST00000302262.8 linkuse as main transcript	c.2331+24T>C		intron_variant		1	NM_000152.5	P1

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

GnomAD3 exomes

AF:

0.149

AC:

36519

AN:

244470

Hom.:

3451

AF XY:

0.152

AC XY:

20234

AN XY:

133082

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 SAS exome

AF:

0.240

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

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0841

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.155

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.143

AC:

21781

AN:

152200

Hom.:

1835

Cov.:

AF XY:

0.145

AC XY:

10783

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.0960

Gnomad4 ASJ

AF:

0.0935

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.121

Hom.:

259

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

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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

-1.0

CADD

Benign

0.17

DANN

Benign

0.36

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