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 obtained from curated document aligns with the Allele Registry but not with ClinVar data

Variant: NM_001754.5(RUNX1):c.705C>T (p.Ala235=)

CA320603683

532686 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0296c915-483d-450c-bd77-48afc65e46a6
Approved on: 2025-02-24
Published on: 2025-02-24

HGVS expressions

NM_001754.5:c.705C>T
NM_001754.5(RUNX1):c.705C>T (p.Ala235=)
NC_000021.9:g.34834510G>A
CM000683.2:g.34834510G>A
NC_000021.8:g.36206807G>A
CM000683.1:g.36206807G>A
NC_000021.7:g.35128677G>A
NG_011402.2:g.1155202C>T
ENST00000675419.1:c.705C>T
ENST00000300305.7:c.705C>T
ENST00000344691.8:c.624C>T
ENST00000358356.9:c.624C>T
ENST00000399237.6:c.669C>T
ENST00000399240.5:c.532+24964C>T
ENST00000437180.5:c.705C>T
ENST00000469087.1:n.241C>T
ENST00000482318.5:c.*295C>T
NM_001001890.2:c.624C>T
NM_001122607.1:c.624C>T
NM_001754.4:c.705C>T
NM_001001890.3:c.624C>T
NM_001122607.2:c.624C>T
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Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 25
PVS1 PM5 PM3 PM1 PM4 PM6 PM2 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP5 BP7 PS1 PS4 PS2 PS3 PP1 PP4 PP3 PP2

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.705C>T (p.Ala235=) is a synonymous variant not predicted to affect splicing (BP4). However, evolutionary conservation prediction algorithms predict the site as being conserved (PhyloP score: 3.88) and the variant is not the reference nucleotide in one primate and/or three mammal species. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4.
Met criteria codes
BP4
Splice AI=0.02
Not Met criteria codes
PVS1
Not a null variant
PM5
Amino acid 235 has not been described as pathogenic before
PM3
Not applicable
PM1
Not located in a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues AA 89-204 .
PM4
No change in protein length
PM6
No case study found
PM2
This variant has a MAF of 0.00004237 (0.004237%) (it is present in 50/1179988 alleles in the European (non-Finnish) population of gnomADv4.1.0
BA1
ALL:0.00071% (2/282376 alleles) - NFE:0.0016% (2) (gnomAD v2) ALL:0.0001397% (2/143146 alleles) - NFE:0.003099% (2) (gnomAD v3)
BS2
Not applicable
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No functional studies found
BS1
ALL:0.00071% (2/282376 alleles) - NFE:0.0016% (2) (gnomAD v2) ALL:0.0001397% (2/143146 alleles) - NFE:0.003099% (2) (gnomAD v3)
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
Not applicable
BP1
Not applicable
BP5
Not applicable
BP7
The nucleotide is evolutionarily conserved (phylopP100 =3.88)
PS1
Amino acid 235 has not been described as pathogenic before
PS4
No proband meeting RUNX1 FPDMM phenotypic criteria has been identified
PS2
No case study found
PS3
No functional studies found
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Not applicable
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
Not applicable
Curation History
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