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.1119G>A (p.Ser373=)

CA512341295

1430658 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0ab08412-874e-4fb5-97e5-67b61f34194d
Approved on: 2024-07-11
Published on: 2024-07-11

HGVS expressions

NM_001754.5:c.1119G>A
NM_001754.5(RUNX1):c.1119G>A (p.Ser373=)
NC_000021.9:g.34792459C>T
CM000683.2:g.34792459C>T
NC_000021.8:g.36164756C>T
CM000683.1:g.36164756C>T
NC_000021.7:g.35086626C>T
NG_011402.2:g.1197253G>A
ENST00000675419.1:c.1119G>A
ENST00000300305.7:c.1119G>A
ENST00000344691.8:c.1038G>A
ENST00000399240.5:c.846G>A
ENST00000437180.5:c.1119G>A
ENST00000482318.5:c.*709G>A
NM_001001890.2:c.1038G>A
NM_001754.4:c.1119G>A
NM_001001890.3:c.1038G>A

Likely Benign

Met criteria codes 3
BP7 BP4 PM2_Supporting
Not Met criteria codes 23
PVS1 BP5 BP3 BP2 BP1 BA1 PS4 PS1 PS2 PS3 PP1 PP4 PP3 PP2 PM6 PM5 PM1 PM4 PM3 BS2 BS4 BS3 BS1

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.1119G>A (p.Ser373=) is a synonymous variant which is not predicted by SpliceAI to impact splicing (BP4); in addition, an evolutionary conservation algorithm predicts the site as being non-conserved (PhyloP score = -0.00400787 in GRCh38), and the variant allele is the reference nucleotide in one primate and/or three mammal species (BP7). Although the variant is absent from gnomAD v2 and v3 (PM2_supporting), it also has not been reported in cases or the literature. In summary, this variant meets the criteria to be classified as likely benign for hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: BP4, BP7, PM2_supporting.
Met criteria codes
BP7
The variant is not predicted by SpliceAI to impact splicing. In addition, an evolutionary conservation algorithm predicts the site as being non-conserved (PhyloP score = -0.00400787 in GRCh38), and the variant allele is the reference nucleotide in one primate and/or three mammal species.
BP4
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
PM2_Supporting
Completely absent from gnomAD with a mean coverage of at least 20X (v2 and v3).
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
Not applicable
BP3
Not applicable
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
Not applicable
BA1
Completely absent from gnomAD with a mean coverage of at least 20X (v2 and v3).
PS4
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PP1
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PP4
Not applicable
PP3
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
PP2
Not applicable
PM6
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PM5
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
PM3
Not applicable
BS2
Not applicable
BS4
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS1
Completely absent from gnomAD with a mean coverage of at least 20X (v2 and v3).
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