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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

Variant: NM_001754.5(RUNX1):c.215_216dup (p.Ser73fs)

CA658656806

463988 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1d884ce0-9d6e-40e7-a2aa-6f0ff56bae4c

HGVS expressions

NM_001754.5:c.215_216dup
NM_001754.5(RUNX1):c.215_216dup (p.Ser73fs)
NC_000021.9:g.34886978_34886979dup
CM000683.2:g.34886978_34886979dup
NC_000021.8:g.36259275_36259276dup
CM000683.1:g.36259275_36259276dup
NC_000021.7:g.35181145_35181146dup
NG_011402.2:g.1102733_1102734dup
ENST00000675419.1:c.215_216dup
ENST00000300305.7:c.215_216dup
ENST00000344691.8:c.134_135dup
ENST00000358356.9:c.134_135dup
ENST00000399237.6:c.179_180dup
ENST00000399240.5:c.134_135dup
ENST00000437180.5:c.215_216dup
ENST00000455571.5:c.176_177dup
ENST00000482318.5:c.59-6266_59-6265dup
NM_001001890.2:c.134_135dup
NM_001122607.1:c.134_135dup
NM_001754.4:c.215_216dup
NM_001001890.3:c.134_135dup
NM_001122607.2:c.134_135dup

Pathogenic

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

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
The NM_001754.4:c.215_216dup (p.Ser73Glyfs) 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; SCV000638134.1). 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
PVS1
Frameshift (+1) variant before the c.779 cutoff that predict to undergo NMD.
PS4_Supporting
One proband with Thrombocytopenia and MDS (SCV000638134.1).
PM2_Supporting
The variant is absent from all population databases.
PM5_Supporting
This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting).
Not Met criteria codes
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
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
PM6
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
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
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
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
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2024-03-26
Published on: 2024-03-26
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