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 computer assertion could be determined for this classification!


Variant: NM_001754.5(RUNX1):c.122C>T (p.Thr41Met)

CA10014590

661459 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 546a3ea3-a27c-46e7-a9a2-463a702bc1bc
Approved on: 2024-08-01
Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.122C>T
NM_001754.5(RUNX1):c.122C>T (p.Thr41Met)
NC_000021.9:g.34887072G>A
CM000683.2:g.34887072G>A
NC_000021.8:g.36259369G>A
CM000683.1:g.36259369G>A
NC_000021.7:g.35181239G>A
NG_011402.2:g.1102640C>T
ENST00000675419.1:c.122C>T
ENST00000300305.7:c.122C>T
ENST00000344691.8:c.41C>T
ENST00000358356.9:c.41C>T
ENST00000399237.6:c.86C>T
ENST00000399240.5:c.41C>T
ENST00000437180.5:c.122C>T
ENST00000455571.5:c.83C>T
ENST00000475045.6:c.122C>T
ENST00000482318.5:c.59-6359C>T
NM_001001890.2:c.41C>T
NM_001122607.1:c.41C>T
NM_001754.4:c.122C>T
NM_001001890.3:c.41C>T
NM_001122607.2:c.41C>T
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Uncertain Significance

Not Met criteria codes 26
PS1 PS2 PS4 PS3 BP7 BP5 BP3 BP2 BP4 BP1 BA1 PP4 PP1 PP3 PP2 PVS1 PM5 PM1 PM4 PM3 PM6 PM2 BS2 BS4 BS3 BS1

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.122C>T (p.Thr41Met) is a missense variant which does not meet any ACMG/AMP criteria. 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: None.
Not Met criteria codes
PS1
PS1 cannot be applied because to our knowledge, there is no other missense variant determined to be pathogenic at this amino acid residue.
PS2
PS2 cannot be applied because there is no data available.
PS4
To our knowledge, this variant has not been reported in the literature in individuals affected with RUNX1-related conditions.
PS3
PS3 cannot be applied because there is no functional data available for this variant.
BP7
BP7 cannot be applied because this variant is a missense variant.
BP5
This rule is not applicable to the MMVCEP.
BP3
This rule is not applicable to the MMVCEP.
BP2
BP2 cannot be applied because there is no data available.
BP4
This missense variant has a REVEL score ≥ 0.50 (0.61) and SpliceAI score is ≤ 0.20 (0).
BP1
This rule is not applicable to the MMVCEP.
BA1
The variant is present in gnomAD v2.1.1 ONLY but does not meet code criteria (MAF 0.000009 (Eur Non-Finnish)
PP4
This rule is not applicable to the MMVCEP.
PP1
PP1 cannot be applied because there is no data available.
PP3
This missense variant has a REVEL score ≤ 0.88 (0.61) and SpliceAI score is ≤ 0.38 (0).
PP2
This rule is not applicable to the MMVCEP.
PVS1
PVS1 cannot be applied because this variant is a missense change.
PM5
PM5 cannot be applied because to our knowledge, there is no other missense variant determined to be pathogenic at this amino acid residue.
PM1
PM1 cannot be applied because this variant is not located in not located in AA residues 89-204.
PM4
PM4 cannot be applied because this variant is a missense variant.
PM3
This rule is not applicable to the MMVCEP.
PM6
PM6 cannot be applied because there is no data available.
PM2
The highest population minor allele frequency in gnomAD v2.1.1 is 0.000009 in Eur Non-Finnish population.
BS2
BS2 is not applicable since FPD/AML patients display incomplete penetrance and the average age of onset of hematologic malignancies is 33 years.
BS4
BS4 cannot be applied because there is no data available.
BS3
BS3 cannot be applied because there is no functional data available for this variant.
BS1
The variant is present in gnomAD v2.1.1 ONLY but does not meet code criteria (MAF 0.000009 (Eur Non-Finnish)
Curation History
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