Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_001111067.4(ACVR1):c.982G>T(p.Gly328Trp) 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. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G328V) has been classified as Uncertain significance.
ACVR1 (HGNC:171): (activin A receptor type 1) Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I ( I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type I receptor which signals a particular transcriptional response in concert with activin type II receptors. Mutations in this gene are associated with fibrodysplasia ossificans progressive. [provided by RefSeq, Jul 2008]
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr2-157766004-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 29595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.959
PP5
Variant 2-157766005-C-A is Pathogenic according to our data. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-157766005-C-A is described in CliVar as Pathogenic. Clinvar id is 29594.Status of the report is no_assertion_criteria_provided, 0 stars.