Variant chr17-80107908-G-A 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.955+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,594,892 control chromosomes in the GnomAD database, including 403,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33494 hom., cov: 33)

Exomes 𝑓: 0.71 ( 370275 hom. )

Consequence

GAA
NM_000152.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:12

Conservation

PhyloP100: -0.701

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=-0.94).

BP6

Variant 17-80107908-G-A is Benign according to our data. Variant chr17-80107908-G-A is described in ClinVar as [Benign]. Clinvar id is 92491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80107908-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.731 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.955+12G>A		intron_variant		ENST00000302262.8	NP_000143.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAA	ENST00000302262.8 linkuse as main transcript	c.955+12G>A		intron_variant		1	NM_000152.5	ENSP00000305692	P1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99600

AN:

151956

Hom.:

33481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.736

Gnomad OTH

AF:

0.668

GnomAD3 exomes

AF:

0.695

AC:

150388

AN:

216458

Hom.:

52770

AF XY:

0.706

AC XY:

83917

AN XY:

118798

show subpopulations

Gnomad AFR exome

AF:

0.579

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.785

Gnomad EAS exome

AF:

0.559

Gnomad SAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.776

Gnomad NFE exome

AF:

0.763

Gnomad OTH exome

AF:

0.735

GnomAD4 exome

AF:

0.714

AC:

1030860

AN:

1442818

Hom.:

370275

Cov.:

AF XY:

0.716

AC XY:

512901

AN XY:

716836

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.513

Gnomad4 ASJ exome

AF:

0.783

Gnomad4 EAS exome

AF:

0.567

Gnomad4 SAS exome

AF:

0.677

Gnomad4 FIN exome

AF:

0.769

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.711

GnomAD4 genome

AF:

0.655

AC:

99644

AN:

152074

Hom.:

33494

Cov.:

AF XY:

0.653

AC XY:

48558

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.531

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.770

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.661

Gnomad4 FIN

AF:

0.776

Gnomad4 NFE

AF:

0.736

Gnomad4 OTH

AF:

0.667

Alfa

AF:

0.710

Hom.:

6878

Bravo

AF:

0.635

Asia WGS

AF:

0.586

AC:

2043

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 04, 2018	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Uncertain:1Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 82.703% in ExAC) based on the frequency threshold of 2.76% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.5 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.A synonymous variant not located in a splice region. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 19, 2015	- -

Glycogen storage disease, type II

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.3

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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