17-80104471-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000152.5(GAA):c.-32-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,012,690 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (82 hom.)
• Consequence: GAA NM_000152.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-80104471-G-A is Benign according to our data. Variant chr17-80104471-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00546 (831/152160) while in subpopulation SAS AF= 0.0467 (225/4818). AF 95% confidence interval is 0.0417. There are 6 homozygotes in gnomad4. There are 465 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAA	NM_000152.5	c.-32-84G>A		intron_variant		ENST00000302262.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAA	ENST00000302262.8	c.-32-84G>A		intron_variant		1	NM_000152.5	P1

Frequencies

GnomAD3 genomes AF: 0.00543 AC: 826 AN: 152042 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00419

Gnomad OTH AF: 0.00672

GnomAD4 exome AF: 0.00659 AC: 5668 AN: 860530 Hom.: 82 AF XY: 0.00791 AC XY: 3413 AN XY: 431236

Gnomad4 AFR exome AF: 0.00399

Gnomad4 AMR exome AF: 0.00202

Gnomad4 ASJ exome AF: 0.000479

Gnomad4 EAS exome AF: 0.000454

Gnomad4 SAS exome AF: 0.0431

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.00388

Gnomad4 OTH exome AF: 0.00715

GnomAD4 genome AF: 0.00546 AC: 831 AN: 152160 Hom.: 6 Cov.: 32 AF XY: 0.00625 AC XY: 465 AN XY: 74392

Gnomad4 AFR AF: 0.00323

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0467

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.00419

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00305 Hom.: 0

Bravo AF: 0.00354

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.0020
Dann	Benign	0.50

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

Other links and lift over

dbSNP: rs368377256; hg19: chr17-78078270;