rs864309492
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_001615.4(ACTG2):c.593G>A(p.Gly198Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G198V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001615.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTG2 | NM_001615.4 | c.593G>A | p.Gly198Asp | missense_variant | 6/9 | ENST00000345517.8 | |
ACTG2 | NM_001199893.2 | c.464G>A | p.Gly155Asp | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTG2 | ENST00000345517.8 | c.593G>A | p.Gly198Asp | missense_variant | 6/9 | 1 | NM_001615.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 35
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Visceral myopathy 1 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | Feb 17, 2017 | The c.593G>A (p.Gly198Asp) variant is a missense variant in the ACTG2 gene. This variant has a previously reported in a patient with megacystis-microcolon-intestinal hypoperistalsis syndrome (PMID: 24676022). This variant is not seen in ExAC database thus it is presumed to be rare. This variant is predicted to be damaging based on in silico modeling. No functional studies exist for this particular variant. Based on the combined evidence and the variant being de novo in this patient, the variant is classified as pathogenic. - |
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Mar 27, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at