Evidence Repository
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 label mismatch: RUNX1 vs undefined
  • 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.444C>T (p.Thr148=)

CA10014514

339877 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2a26c020-4ebb-4160-a16b-4c5b8b5b9440
Approved on: 2025-03-26
Published on: 2025-03-26

HGVS expressions

NM_001754.5:c.444C>T
NM_001754.5(RUNX1):c.444C>T (p.Thr148=)
NC_000021.9:g.34880621G>A
CM000683.2:g.34880621G>A
NC_000021.8:g.36252918G>A
CM000683.1:g.36252918G>A
NC_000021.7:g.35174788G>A
NG_011402.2:g.1109091C>T
ENST00000675419.1:c.444C>T
ENST00000300305.7:c.444C>T
ENST00000344691.8:c.363C>T
ENST00000358356.9:c.363C>T
ENST00000399237.6:c.408C>T
ENST00000399240.5:c.363C>T
ENST00000437180.5:c.444C>T
ENST00000455571.5:c.405C>T
ENST00000482318.5:c.*34C>T
NM_001001890.2:c.363C>T
NM_001122607.1:c.363C>T
NM_001754.4:c.444C>T
NM_001001890.3:c.363C>T
NM_001122607.2:c.363C>T
More

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 24
BP5 BP2 BP3 BP1 PS2 PS4 PS1 PS3 BA1 PP4 PP1 PP3 PP2 PM6 PM2 PM3 PM5 PM1 PM4 PVS1 BS4 BS1 BS3 BS2

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.444C>T (p.Thr148=) is a synonymous variant which has a SpliceAI score of 0.00 and a PhyloP score of -6.58, indicating no predicted impact on splicing and lack of conservation (BP4, BP7). This variant is present in gnomAD but not at an elevated frequency, so no population codes were applied. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.
Met criteria codes
BP7
This variant has a SpliceAI score ≤ 0.20 (0) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score = (-6.58)) (BP7).
BP4
This synonymous or intronic variant has a SpliceAI score ≤ 0.20 (0.0) (BP4).
Not Met criteria codes
BP5
This rule is not applicable for RUNX1.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
This rule is not applicable for RUNX1
BP1
This rule is not applicable for RUNX1.
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.
PS1
There has not yet been a missense change determined to be pathogenic at this amino acid residue.
PS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
BA1
This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
PP4
This rule is not applicable for RUNX1.
PP1
Segregation data for this variant has not been reported in literature.
PP3
This synonymous variant does not have a SpliceAI score ≥ 0.38.
PP2
This rule is not applicable for RUNX1.
PM6
De novo data for this variant has not been reported in literature.
PM2
This variant is present in at least one population database.
PM3
This rule is not applicable for RUNX1.
PM5
There has not yet been a different missense change determined to be pathogenic at this amino acid residue.
PM1
This variant is not a missense variant.
PM4
This variant is not an in-frame deletion/insertion.
PVS1
This variant is not a null variant.
BS4
Segregation data for this variant has not been reported in literature.
BS1
This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.
BS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
BS2
This rule is not applicable for RUNX1.
Curation History
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