LYFE Sciences · Project HERA
Variant Interpretation · Classification Report
Generated: 2026-08-13
Case ID: NM_001042749.1_c.2431G_T_20260813_205233
Framework: ACMG/AMP 2015
Variant classification summary

NM_001042749.1:c.2431G>T

STAG2  · NP_001036214.1:p.(Glu811Ter)  · NM_001042749.1
GRCh37: chrX:123205071 G>T  ·  GRCh38: chrX:124071221 G>T
Gene: STAG2 Transcript: NM_001042749.1
Final call
VUS
PM2 supporting
All criteria require review: For research and educational purposes only.
Variant details
Gene
STAG2
Transcript
NM_001042749.1
Protein
NP_001036214.1:p.(Glu811Ter)
gnomAD AF
ClinVar
OncoKB
Likely Oncogenic
Classification rationale
Interpretation summary
Generated evidence synthesis
1
PM2 (Supporting): variant absent from gnomAD v2.1, v4.1 (~800K alleles), and gnomAD-Canada v1.0 (AF = 0).
2
VUS: the single supporting criterion (PM2) satisfies no combination rule in the generic ACMG/AMP 2015 fallback.
Final determination: Under the generic ACMG/AMP 2015 fallback combination rules, a single supporting criterion (PM2) does not reach any Pathogenic, Likely Pathogenic, Benign, or Likely Benign threshold, so the variant is classified as Variant of Uncertain Significance.
Criteria assessment
ACMG/AMP criteria review
Criteria shown when status is available
All criteria require review: For research and educational purposes only.
Criterion Status Rationale Evidence used
PVS1 Not assessed Not assessed: insufficient evidence was available to evaluate a predicted loss-of-function effect.
PS1 N/A Not applicable: a nonsense variant creates no altered amino acid to compare with a previously pathogenic missense change.
generic_acmg_combination_rules
PS2 Not assessed Not assessed: no proband clinical data or parental-genotype confirmation exist to evaluate a de novo origin.
generic_acmg_combination_rules clinvar
PS3 Not assessed Not assessed: no well-established functional assay of this exact variant was available.
generic_acmg_combination_rules oncokb PMID:21852505 PMID:22417201 PMID:24121789 PMID:25010205
PS4 Not met Not met: no case-control enrichment data exist; the variant is absent from ClinVar, gnomAD, and COSMIC.
clinvar gnomad_v2 gnomad_v4 oncokb PMID:21852505 PMID:22417201 PMID:24121789 PMID:25010205
PM1 N/A Not applicable: a nonsense variant produces no altered residue to assess for a mutational hotspot.
generic_acmg_combination_rules
PM2 Met Met (supporting): absent from gnomAD v2.1, v4.1 (~800,000 alleles), and gnomAD-Canada v1.0.
gnomad_v2 gnomad_v4 gnomad_canada generic_acmg_combination_rules pvs1_gene_context
PM3 Not assessed Not assessed: no phase or biallelic observations in affected individuals are available.
generic_acmg_combination_rules clinvar
PM4 N/A Not applicable: a nonsense variant causes no protein length change for this criterion to evaluate.
pvs1_generic_framework generic_acmg_combination_rules
PM5 N/A Not applicable: no missense change exists at this residue, so none can be compared to a known pathogenic missense.
generic_acmg_combination_rules
PM6 Not assessed Not assessed: no proband observation or parental testing exists to support an assumed de novo origin.
generic_acmg_combination_rules clinvar
PP1 Not assessed Not assessed: no family members are genotyped, so no meioses are available to score segregation.
generic_acmg_combination_rules clinvar
PP2 N/A Not applicable: missense-constraint evidence is irrelevant because no missense change is present.
generic_acmg_combination_rules
PP3 Not met Not met: SpliceAI max delta 0.033 is far below the >0.2 splice-altering threshold.
generic_acmg_combination_rules spliceai bayesdel
PP4 Not assessed Not assessed: no proband phenotype or family-history data are available to evaluate phenotype specificity.
PP5 Not met Not met: the variant has no ClinVar record, so no expert-panel pathogenic classification exists to trigger PP5.
clinvar oncokb
BA1 Not met Not met: allele frequency is 0 in gnomAD, far below the >5% BA1 threshold.
gnomad_v2 gnomad_v4 gnomad_canada generic_acmg_combination_rules
BS1 Not met Not met: absent from gnomAD (AF 0), below the >0.3% expected-frequency threshold.
gnomad_v2 gnomad_v4 gnomad_canada generic_acmg_combination_rules pvs1_gene_context
BS2 Not met Not met: no observations in healthy adults exist, the opposite of what BS2 requires.
gnomad_v2 gnomad_v4 gnomad_canada clinvar
BS3 Not assessed Not assessed: no functional study demonstrates retained STAG2 function or normal splicing.
generic_acmg_combination_rules oncokb PMID:21852505 PMID:22417201 PMID:24121789 PMID:25010205
BS4 Not assessed Not assessed: no family members are genotyped, so non-segregation cannot be documented.
generic_acmg_combination_rules clinvar
BP1 N/A Not applicable: no missense change exists, so the truncating-mechanism context does not apply.
generic_acmg_combination_rules
BP2 Not assessed Not assessed: no second variant is observed in cis or trans, and no phase information exists.
generic_acmg_combination_rules clinvar
BP3 N/A Not applicable: a nonsense variant does not alter protein length within a repetitive region.
pvs1_generic_framework generic_acmg_combination_rules
BP4 Not met Not met: the stop-gain itself is an impact on the gene product; SpliceAI (0.033) does not negate it.
generic_acmg_combination_rules spliceai bayesdel
BP5 Not assessed Not assessed: no proband-level data exist to determine an alternate molecular basis of disease.
BP6 Not met Not met: the variant has no ClinVar record, so no expert-panel benign classification exists to trigger BP6.
clinvar oncokb
BP7 N/A Not applicable: BP7 requires a synonymous variant; this is a nonsense substitution.
generic_acmg_combination_rules
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