17-80101663-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000152.5(GAA):c.-260G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,788 control chromosomes in the GnomAD database, including 2,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2727 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: GAA NM_000152.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.528

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-80101663-G-C is Benign according to our data. Variant chr17-80101663-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 325769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAA	NM_000152.5	c.-260G>C		5_prime_UTR_variant	1/20	ENST00000302262.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAA	ENST00000302262.8	c.-260G>C		5_prime_UTR_variant	1/20	1	NM_000152.5	P1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25639 AN: 151578 Hom.: 2726 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.104 AC: 10 AN: 96 Hom.: 0 Cov.: 0 AF XY: 0.0781 AC XY: 5 AN XY: 64

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.169 AC: 25629 AN: 151692 Hom.: 2727 Cov.: 32 AF XY: 0.166 AC XY: 12278 AN XY: 74144

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0545

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.190

Alfa AF: 0.112 Hom.: 193

Bravo AF: 0.163

Asia WGS AF: 0.0850 AC: 295 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Glycogen storage disease, type II Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.6
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2304849; hg19: chr17-78075462;