[Paper-level Aggregated] PMCID: PMC7211323

Evidence Type(s): Oncogenic, Functional, Predictive

Justification: Oncogenic: The text indicates that mutations in the ACVR2A gene, particularly c.1309-1310delAA and c.285delA, are associated with a high mutation frequency and are prevalent in MSI-H gastric cancers, suggesting a role in tumorigenesis. Functional: The in vitro experiments demonstrate that ACVR2A mutations lead to altered protein expression and stability, indicating that these mutations have functional consequences on the gene product. Predictive: The association of ACVR2A mutations with MSI-H status suggests that these mutations could predict the microsatellite instability phenotype in gastric cancer patients.

Gene→Variant (gene-first): ACVR2A(92):1309-1310delAA ACVR2A(92):c.1310delA ACVR2A(92):c.285delA ACVR2A(92):1310AA ACVR2A(92):1310delA ACVR2A(92):c.1309-1310delAA ACVR2A(92):p. D96Tfs*54

Genes: ACVR2A(92)

Variants: 1309-1310delAA c.1310delA c.285delA 1310AA 1310delA c.1309-1310delAA p. D96Tfs*54

[Paragraph-level] PMCID: PMC7211323 Section: RESULTS PassageIndex: 11

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage discusses how the ACVR2A variants (including c.285delA) affect the expression and stability of the ACVR2A protein, indicating that these variants alter molecular function. Oncogenic: The context of the study involves the role of ACVR2A mutations in gastric cancer (GC) cell lines, suggesting that these somatic variants may contribute to tumor development or progression.

Gene→Variant (gene-first): 92:1310AA 92:c.285delA

Genes: 92

Variants: 1310AA c.285delA

[Paragraph-level] PMCID: PMC7211323 Section: RESULTS PassageIndex: 9

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the mutation rate of ACVR2A in a specific population and identifies specific mutations as frequent occurrences in gastric cancer patients, indicating their association with the disease. Oncogenic: The passage describes nonsynonymous mutations in the ACVR2A gene that lead to protein changes, specifically mentioning frameshift truncating mutations, which contribute to tumor development in gastric cancer.

Gene→Variant (gene-first): 92:1310delA 92:c.1309-1310delAA 92:c.285delA 92:p. D96Tfs*54

Genes: 92

Variants: 1310delA c.1309-1310delAA c.285delA p. D96Tfs*54

[Paragraph-level] PMCID: PMC7211323 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses the association of specific mutations (c.1310delA, 1309-1310delAA, c.285delA) with the MSI-H subtype of gastric cancers, indicating their role in defining or classifying the disease. Oncogenic: The variants mentioned are associated with a high mutation frequency and a high MSI score, suggesting their contribution to tumor development or progression in gastric cancer.

Gene→Variant (gene-first): 92:1309-1310delAA 92:c.1310delA 92:c.285delA

Genes: 92

Variants: 1309-1310delAA c.1310delA c.285delA