chr17-80118320-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000152.5(GAA):c.2609G>C(p.Arg870Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R870Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
GAA
NM_000152.5 missense
NM_000152.5 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: -0.390
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAA | NM_000152.5 | c.2609G>C | p.Arg870Pro | missense_variant | 18/20 | ENST00000302262.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAA | ENST00000302262.8 | c.2609G>C | p.Arg870Pro | missense_variant | 18/20 | 1 | NM_000152.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2023 | The p.R870P variant (also known as c.2609G>C), located in coding exon 17 of the GAA gene, results from a G to C substitution at nucleotide position 2609. The arginine at codon 870 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Loss of solvent accessibility (P = 0.0703);Loss of solvent accessibility (P = 0.0703);
MVP
MPC
0.16
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at