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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  • 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.356dup (p.Ala120fs)

CA645607413

2746077 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 14e1f6d7-fae8-4f15-b604-e77ad9028e46
Approved on: 2024-08-28
Published on: 2024-08-28

HGVS expressions

NM_001754.5:c.356dup
NM_001754.5(RUNX1):c.356dup (p.Ala120fs)
NC_000021.9:g.34880709dup
CM000683.2:g.34880709dup
NC_000021.8:g.36253006dup
CM000683.1:g.36253006dup
NC_000021.7:g.35174876dup
NG_011402.2:g.1109003dup
ENST00000675419.1:c.356dup
ENST00000300305.7:c.356dup
ENST00000344691.8:c.275dup
ENST00000358356.9:c.275dup
ENST00000399237.6:c.320dup
ENST00000399240.5:c.275dup
ENST00000437180.5:c.356dup
ENST00000455571.5:c.317dup
ENST00000482318.5:c.63dup
NM_001001890.2:c.275dup
NM_001122607.1:c.275dup
NM_001754.4:c.356dup
NM_001001890.3:c.275dup
NM_001122607.2:c.275dup

Likely Pathogenic

Met criteria codes 4
PM5_Supporting PVS1_Strong PS4_Moderate PM2_Supporting
Not Met criteria codes 22
PP1 PP4 PP3 PP2 BA1 PM1 PM4 PM3 PM6 BS2 BS4 BS3 BS1 PS2 PS3 PS1 BP4 BP1 BP3 BP2 BP7 BP5

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.356dup (p.Ala120GlyfsTer18) is a frameshift variant which is not predicted to undergo nonsense-mediated decay (NMD), and the truncated/altered region is critical for protein function (PVS1_Strong). This variant is downstream of c.98 (PM5_supporting). It is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant has been reported in at least two probands meeting RUNX1-phenotypic criteria (PS4_Moderate). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_Strong, PM5_supporting, PM2_supporting, PS4_Moderate.
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_Moderate
2-3 probands in literature
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).
Not Met criteria codes
PP1
No case studies found
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
BA1
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
BS2
This rule is not applicable for MM-VCEP
BS4
No case studies found
BS3
No functional studies found
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
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
BP7
Not a synonymous variant
BP5
This rule is not applicable for MM-VCEP
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