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]
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Variant: NM_001754.5(RUNX1):c.146del (p.Pro49fs)

CA2580098653

2101398 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9551370c-8c13-40d8-a7d3-826d90697dd6
Approved on: 2024-09-10
Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.146del
NM_001754.5(RUNX1):c.146del (p.Pro49fs)
NC_000021.9:g.34887050del
CM000683.2:g.34887050del
NC_000021.8:g.36259347del
CM000683.1:g.36259347del
NC_000021.7:g.35181217del
NG_011402.2:g.1102664del
ENST00000675419.1:c.146del
ENST00000300305.7:c.146del
ENST00000344691.8:c.65del
ENST00000358356.9:c.65del
ENST00000399237.6:c.110del
ENST00000399240.5:c.65del
ENST00000437180.5:c.146del
ENST00000455571.5:c.107del
ENST00000475045.6:c.146del
ENST00000482318.5:c.59-6335del
NM_001001890.2:c.65del
NM_001122607.1:c.65del
NM_001754.4:c.146del
NM_001001890.3:c.65del
NM_001122607.2:c.65del

Pathogenic

Met criteria codes 4
PM5_Supporting PVS1_Strong PS4 PM2_Supporting
Not Met criteria codes 22
BA1 BP7 BP5 BP4 BP1 BP3 BP2 BS4 BS3 BS1 BS2 PP1 PP4 PP3 PP2 PS2 PS3 PS1 PM1 PM4 PM3 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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.146del (p.Pro49GlnfsTer4) is a nonsense variant which is not predicted to undergo NMD, and the truncated/altered region is critical for protein function (nonsense c.917-c.1440 as per VCEP specifications) (PVS1_Strong). This variant has been reported in four or more probands meeting at least one of the RUNX1-phenotypic criteria (PS4). It is absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is located downstream of c.98 (PM5_supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_Strong, PM2_supporting, PM5_supporting, PS4.
Met criteria codes
PM5_Supporting
Nonsense variant is located downstream of c.98 (in transcript NM_001754.4).
PVS1_Strong
As per modified RUNX1 PVS1 decision tree
PS4
≥ 4 probands meeting at least one of the RUNX1-phenotypic criteria.
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
Not a synonymous variant
BP5
This rule is not applicable for MM-VCEP
BP4
Not a missense variant
BP1
This rule is not applicable for MM-VCEP
BP3
This rule is not applicable for MM-VCEP
BP2
No case studies found
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
This rule is not applicable for MM-VCEP
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
This rule is not applicable for MM-VCEP
PP3
This variant does not have applicable in-silico data available. This is a not a missense, synonymous, or intronic variant.
PP2
This rule is not applicable for MM-VCEP
PS2
Information not available
PS3
No functional studies found
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
This variant is not a missense variant.
PM4
Nonsense variant
PM3
This rule is not applicable for MM-VCEP.
PM6
Not reported
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