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]

Variant: NM_001754.5(RUNX1):c.442_449del (p.Thr148fs)

CA248627

14470 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 029c6661-002e-49de-a67f-e2903b825e5b
Approved on: 2024-03-26
Published on: 2024-03-26

HGVS expressions

NM_001754.5:c.442_449del
NM_001754.5(RUNX1):c.442_449del (p.Thr148fs)
NC_000021.9:g.34880616_34880623del
CM000683.2:g.34880616_34880623del
NC_000021.8:g.36252913_36252920del
CM000683.1:g.36252913_36252920del
NC_000021.7:g.35174783_35174790del
NG_011402.2:g.1109089_1109096del
ENST00000675419.1:c.442_449del
ENST00000300305.7:c.442_449del
ENST00000344691.8:c.361_368del
ENST00000358356.9:c.361_368del
ENST00000399237.6:c.406_413del
ENST00000399240.5:c.361_368del
ENST00000437180.5:c.442_449del
ENST00000455571.5:c.403_410del
ENST00000482318.5:c.*32_*39del
NM_001001890.2:c.361_368del
NM_001122607.1:c.361_368del
NM_001754.4:c.442_449del
NM_001001890.3:c.361_368del
NM_001122607.2:c.361_368del
More

Pathogenic

Met criteria codes 4
PS4_Supporting PM2_Supporting PVS1 PM5_Supporting
Not Met criteria codes 22
BA1 BS2 BS4 BS1 BS3 BP5 BP7 BP2 BP3 BP4 BP1 PS2 PS3 PS1 PP4 PP1 PP3 PP2 PM6 PM3 PM1 PM4

Evidence Links 1

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
The NM_001754.4(RUNX1):c.442_449delACCGCAGC (p.Thr148Hisfs) variant is a frameshift variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 27112265). 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, PM2_supporting, PS4_Supporting, PM5_supporting.
Met criteria codes
PS4_Supporting
One family with FPD/AML.
One family with FPD/AML. PubMed:27112265
PM2_Supporting
The variant is absent from all population databases.
PVS1
Frameshift (+1) variant before the c.779 cutoff that predict to undergo NMD.
PM5_Supporting
This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting).
Not Met criteria codes
BA1
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
One meiosis PubMed:27112265
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
One meiosis
One meiosis PubMed:27112265
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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