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]
  • 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.1215G>A (p.Leu405=)

CA512341219

463979 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f214e189-eb3f-4c62-8a56-6023bfeb1573
Approved on: 2024-07-11
Published on: 2024-07-11

HGVS expressions

NM_001754.5:c.1215G>A
NM_001754.5(RUNX1):c.1215G>A (p.Leu405=)
NC_000021.9:g.34792363C>T
CM000683.2:g.34792363C>T
NC_000021.8:g.36164660C>T
CM000683.1:g.36164660C>T
NC_000021.7:g.35086530C>T
NG_011402.2:g.1197349G>A
ENST00000675419.1:c.1215G>A
ENST00000300305.7:c.1215G>A
ENST00000344691.8:c.1134G>A
ENST00000399240.5:c.942G>A
ENST00000437180.5:c.1215G>A
ENST00000482318.5:c.*805G>A
NM_001001890.2:c.1134G>A
NM_001754.4:c.1215G>A
NM_001001890.3:c.1134G>A
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 24
PP1 PP4 PP3 PP2 PM6 PM2 PM3 PM1 PM5 PM4 PS4 PS3 PS2 PS1 BA1 PVS1 BP2 BP3 BP1 BP5 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.1215G>A (p.Leu405=) is a synonymous variant which is located at a non-conserved nucleotide per an evolutionary conservation algorithm (PhyloP score = -0.00400787 in GRCh38); it is not predicted to have any splicing impact per SpliceAI (BP7, BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.
Met criteria codes
BP4
SpliceAI does not show any significant splicing impact (Δ scores ≤ 0.20).
BP7
Synonymous variant located at a non-conserved nucleotide (PhyloP = -0.00400787 in GRCh38), although the variant is not the reference nucleotide in one primate and/or 3 mammals. SpliceAI does not show a splicing impact.
Not Met criteria codes
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Not applicable
PP3
SpliceAI does not show any significant splicing impact (Δ scores ≤ 0.20).
PP2
Not applicable
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
gnomAD v2: ALL: 0.0005947% (1/168166) - NFE: 0.001476% (1/67732) gnomAD v3: absent with ≥20x coverage
PM3
Not applicable
PM1
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
PS4
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
PS2
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
BA1
MAF<0.15% gnomAD v2: ALL: 0.0005947% (1/168166) - NFE: 0.001476% (1/67732) gnomAD v3: absent with ≥20x coverage
PVS1
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
Not applicable
BP1
Not applicable
BP5
Not applicable
BS2
Not applicable
BS4
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
BS1
MAF<0.015% gnomAD v2: ALL: 0.0005947% (1/168166) - NFE: 0.001476% (1/67732) gnomAD v3: absent with ≥20x coverage
Curation History
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