The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_001754.5(RUNX1):c.527C>A (p.Thr176Asn)

CA410208119

1512969 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: ee456599-10ab-49e7-bcb5-a6d09ff23902
Approved on: 2024-09-25
Published on: 2024-09-25

HGVS expressions

NM_001754.5:c.527C>A
NM_001754.5(RUNX1):c.527C>A (p.Thr176Asn)
NC_000021.9:g.34859560G>T
CM000683.2:g.34859560G>T
NC_000021.8:g.36231857G>T
CM000683.1:g.36231857G>T
NC_000021.7:g.35153727G>T
NG_011402.2:g.1130152C>A
ENST00000675419.1:c.527C>A
ENST00000300305.7:c.527C>A
ENST00000344691.8:c.446C>A
ENST00000358356.9:c.446C>A
ENST00000399237.6:c.491C>A
ENST00000399240.5:c.446C>A
ENST00000437180.5:c.527C>A
ENST00000467577.1:n.19C>A
ENST00000482318.5:c.*117C>A
NM_001001890.2:c.446C>A
NM_001122607.1:c.446C>A
NM_001754.4:c.527C>A
NM_001001890.3:c.446C>A
NM_001122607.2:c.446C>A
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Uncertain Significance

Met criteria codes 3
PP3 PM2_Supporting PM1_Supporting
Not Met criteria codes 23
BA1 PM5 PM3 PM4 PM6 PS2 PS4 PS3 PS1 PP1 PP4 PP2 PVS1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP7 BP5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.527C>A (p.Thr176Asn) is a missense variant which has a REVEL score ≥ 0.88 (0.94) (PP3). This variant affects a residue within the Runt Homology domain (AA 89-294) but does not impact a residue which has been established as a hotspot (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PP3, PM1_supporting, PM2_supporting.
Met criteria codes
PP3
This missense variant has a REVEL score ≥ 0.88 (0.94) (PP3).
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).
PM1_Supporting
This variant affects one of the other residues (AA 89-204) within the RHD (PM1_Supporting).
Not Met criteria codes
BA1
This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
PM5
There has not yet been a different missense change determined to be pathogenic at this amino acid residue.
PM3
This rule is not applicable for MM-VCEP.
PM4
This variant is not an in-frame deletion/insertion.
PM6
De novo data for this variant has not been reported in literature.
PS2
De novo data for this variant has not been reported in literature.
PS4
Proband data for this variant has not been reported in literature.
PS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
PS1
There has not yet been a missense change determined to be pathogenic at this amino acid residue.
PP1
Segregation data for this variant has not been reported in literature.
PP4
This rule is not applicable for MM-VCEP.
PP2
This rule is not applicable for MM-VCEP.
PVS1
This variant is not a null variant.
BS2
This rule is not applicable for MM-VCEP.
BS4
Segregation data for this variant has not been reported in literature.
BS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
BS1
This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.
BP2
This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
BP3
This rule is not applicable for MM-VCEP.
BP4
This missense variant does not have a REVEL score < 0.50.
BP1
This rule is not applicable for MM-VCEP.
BP7
This variant is not a synonymous or intronic variant.
BP5
This rule is not applicable for MM-VCEP.
Curation History
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