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.848A>C (p.Gln283Pro)

CA410150175

1479269 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 4cab7b3e-1f7a-424d-89ae-71259711530b
Approved on: 2025-01-15
Published on: 2025-01-15

HGVS expressions

NM_001754.5:c.848A>C
NM_001754.5(RUNX1):c.848A>C (p.Gln283Pro)
NC_000021.9:g.34799420T>G
CM000683.2:g.34799420T>G
NC_000021.8:g.36171717T>G
CM000683.1:g.36171717T>G
NC_000021.7:g.35093587T>G
NG_011402.2:g.1190292A>C
ENST00000675419.1:c.848A>C
ENST00000300305.7:c.848A>C
ENST00000344691.8:c.767A>C
ENST00000399240.5:c.575A>C
ENST00000437180.5:c.848A>C
ENST00000482318.5:c.*438A>C
NM_001001890.2:c.767A>C
NM_001754.4:c.848A>C
NM_001001890.3:c.767A>C
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Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting
Not Met criteria codes 24
BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 PS2 PS4 PS3 PS1 PVS1 BA1 PP4 PP1 PP3 PP2 PM3 PM1 PM4 PM5 PM6

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

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.848A>C (p.Gln283Pro) is a missense variant in exon 8 of 9, not located in a hotspot or the RHD domain. It is not predicted to affect splicing or protein function ( REVEL score 0.355, SplicaAI score 0.01 ). The variant is absent from population databases. There is no available literature. In summary, the clinical significance of this variant remains uncertain due to insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4.
Met criteria codes
BP4
This missense variant has a REVEL score < 0.50 (0.355) and a SpliceAI score ≤ 0.20 (0.01) (BP4).
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).
Not Met criteria codes
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.
BS2
not applicable
BP5
not applicable
BP7
This is not a synonymous variant.
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
Not applicable.
BP1
not applicable
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.
PVS1
This is not a null variant.
BA1
This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
PP4
not applicable
PP1
Segregation data for this variant has not been reported in literature.
PP3
This missense variant does not have a REVEL score of ≥ 0.88.
PP2
not applicable
PM3
not applicable
PM1
This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.
PM4
This is not an in/del variant.
PM5
There has not yet been a different missense change determined to be pathogenic at this amino acid residue
PM6
De novo data for this variant has not been reported in literature.
Curation History
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