rs1057516704
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000152.5(GAA):βc.2495_2496delβ(p.Thr832AsnfsTer51) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000685 in 1,460,774 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. L831L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000152.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAA | NM_000152.5 | c.2495_2496del | p.Thr832AsnfsTer51 | frameshift_variant | 18/20 | ENST00000302262.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAA | ENST00000302262.8 | c.2495_2496del | p.Thr832AsnfsTer51 | frameshift_variant | 18/20 | 1 | NM_000152.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460774Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726682
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Glycogen storage disease, type II Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 21, 2021 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370706). This premature translational stop signal has been observed in individual(s) with Pompe disease (PMID: 22644586, 25741864, 31342611). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr832Asnfs*51) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 29, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 06, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at