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]
Link to SEPIO compliant JSON-LD document
  • 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.136G>A (p.Ala46Thr)

CA410204199

1003215 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f6f84fbc-cd4e-4d73-944e-f90ad096c0b8
Approved on: 2024-08-01
Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.136G>A
NM_001754.5(RUNX1):c.136G>A (p.Ala46Thr)
NC_000021.9:g.34887058C>T
CM000683.2:g.34887058C>T
NC_000021.8:g.36259355C>T
CM000683.1:g.36259355C>T
NC_000021.7:g.35181225C>T
NG_011402.2:g.1102654G>A
ENST00000675419.1:c.136G>A
ENST00000300305.7:c.136G>A
ENST00000344691.8:c.55G>A
ENST00000358356.9:c.55G>A
ENST00000399237.6:c.100G>A
ENST00000399240.5:c.55G>A
ENST00000437180.5:c.136G>A
ENST00000455571.5:c.97G>A
ENST00000475045.6:c.136G>A
ENST00000482318.5:c.59-6345G>A
NM_001001890.2:c.55G>A
NM_001122607.1:c.55G>A
NM_001754.4:c.136G>A
NM_001001890.3:c.55G>A
NM_001122607.2:c.55G>A

Uncertain Significance

Met criteria codes 2
BP4 PM2_Supporting
Not Met criteria codes 24
BP5 BP7 BP2 BP3 BP1 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PVS1 BA1 PM6 PM3 PM1 PM4 PM5 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.136G>A (p.Ala46Thr) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This missense variant has a REVEL score <0.50 (0.387) and a SpliceAI score ≤0.20 (0) (BP4). ClinVar has one entry (Invitae, variation ID 1003215) for this variant, but the affected status is unknown. To our knowledge, this variant has not been reported in the literature in individuals affected with RUNX1-related conditions. 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: PM2_supporting, BP4.
Met criteria codes
BP4
This missense variant has a REVEL score <0.50 (0.387) and a SpliceAI score ≤ 0.20 (0) (BP4).
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting).
Not Met criteria codes
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
This rule is not applicable to the MMVCEP.
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Clinvar has one entry (Invitae) for this variant but the affected status is unknown (variation ID 1003215). To our knowledge, no publication has reported this information/variant to date.
PS3
To our knowledge, this variant was not evaluated in transactivation assays.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
This rule is not applicable to the MMVCEP.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
This variant does not reside within a region of RUNX1 that is defined as a mutational hotspot or critical functional domain by the ClinGen MMVCEP.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
To our knowledge, this variant was not evaluated in transactivation assays.
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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