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.351+1G>C

CA16616270

409822 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 5671cfda-4808-4020-8702-22f1816745bd
Approved on: 2024-09-11
Published on: 2024-09-11

HGVS expressions

NM_001754.5:c.351+1G>C
NM_001754.5(RUNX1):c.351+1G>C
NC_000021.9:g.34886842C>G
CM000683.2:g.34886842C>G
NC_000021.8:g.36259139C>G
CM000683.1:g.36259139C>G
NC_000021.7:g.35181009C>G
NG_011402.2:g.1102870G>C
ENST00000675419.1:c.351+1G>C
ENST00000300305.7:c.351+1G>C
ENST00000344691.8:c.270+1G>C
ENST00000358356.9:c.270+1G>C
ENST00000399237.6:c.315+1G>C
ENST00000399240.5:c.270+1G>C
ENST00000437180.5:c.351+1G>C
ENST00000455571.5:c.312+1G>C
ENST00000482318.5:c.59-6129G>C
NM_001001890.2:c.270+1G>C
NM_001122607.1:c.270+1G>C
NM_001754.4:c.351+1G>C
NM_001001890.3:c.270+1G>C
NM_001122607.2:c.270+1G>C

Uncertain Significance

Met criteria codes 2
PM2_Supporting PVS1
Not Met criteria codes 24
BA1 PP4 PP1 PP3 PP2 PM3 PM1 PM4 PM5 PM6 BS2 BS4 BS1 BS3 PS2 PS4 PS3 PS1 BP2 BP3 BP4 BP1 BP5 BP7

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(RUNX1):c.351+1G>C variant is a canonical splice site variant that is predicted to introduce a frameshift and 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). 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, PM2_supporting.
Met criteria codes
PM2_Supporting
The variant is absent from all population databases.
PVS1
A variant at canonical splice site (+1). The transcription predicts to skip exon 4 and generates a frameshift (-1) that predicts to undergo NMD.
Not Met criteria codes
BA1
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
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
PM5
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
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
SCV000550165.2: germline status not confirmed. SCV000807778.1: insufficient data
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
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
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