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]
  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.442_449delACCGCAGC (p.Thr148Hisfs)

CA248627

14470 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 029c6661-002e-49de-a67f-e2903b825e5b
Approved on: 2019-08-01
Published on: 2019-08-02

HGVS expressions

NM_001754.4:c.442_449delACCGCAGC
NM_001754.4(RUNX1):c.442_449delACCGCAGC (p.Thr148Hisfs)
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
NM_001754.5:c.442_449del
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Pathogenic

Met criteria codes 3
PVS1 PS4_Supporting PM2
Not Met criteria codes 23
BA1 BS1 BS4 BS3 BS2 BP4 BP3 BP1 BP2 BP5 BP7 PS1 PS2 PS3 PP1 PP2 PP3 PP4 PM6 PM1 PM3 PM5 PM4

Evidence Links 1

Expert Panel

Criteria Specification Information

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). 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, PS4_Supporting.
Met criteria codes
PVS1
Frameshift (+1) variant before the c.779 cutoff that predict to undergo NMD.
PS4_Supporting
One family with FPD/AML.
One family with FPD/AML. PubMed:27112265
PM2
The variant is absent from all population databases.
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
One meiosis PubMed:27112265
BS3
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
BP4
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
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
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
PS1
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
PP1
One meiosis
One meiosis PubMed:27112265
PP2
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
PP4
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
PM1
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
PM5
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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