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LYFE SCIENCES
Project: HERA
NM_005089.3:c.812A>G
p.Tyr271Cys  ·  ZRSR2
ACMG/AMP
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Initialising…
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Legacy Engine
Processing…
Classification rationale
1

The ZRSR2 c.812A>G (p.Tyr271Cys; p.Y271C) variant has not been reported in ClinVar.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity in population databases and meeting PM2 at supporting strength.

gnomad_v2 ↗ gnomad_v4 ↗
3

Generic PVS1 is not supported because this is a missense substitution rather than a predicted null variant, although gene-level evidence supports loss of function as a disease mechanism for ZRSR2.

pvs1_generic_framework ↗
4

Computational evidence is not sufficient for a definitive missense prediction: SpliceAI predicts no significant splice effect with a maximum delta score of 0.08, while BayesDel is 0.588005.

spliceai ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
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—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. ZRSR2, a splicing factor, is altered in various hematological malignancies.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.08). BayesDel score = 0.588005.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueY271
Hotspots ↗