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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Variant: NM_001754.5(RUNX1):c.1275G>A (p.Pro425=)

CA10587358

258183 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 23ae6c1f-ffcd-4b6e-b6be-45a90e5f9506
Approved on: 2022-07-05
Published on: 2022-07-05

HGVS expressions

NM_001754.5:c.1275G>A
NM_001754.5(RUNX1):c.1275G>A (p.Pro425=)
NC_000021.9:g.34792303C>T
CM000683.2:g.34792303C>T
NC_000021.8:g.36164600C>T
CM000683.1:g.36164600C>T
NC_000021.7:g.35086470C>T
NG_011402.2:g.1197409G>A
ENST00000675419.1:c.1275G>A
ENST00000300305.7:c.1275G>A
ENST00000344691.8:c.1194G>A
ENST00000399240.5:c.1002G>A
ENST00000437180.5:c.1275G>A
ENST00000482318.5:c.*865G>A
NM_001001890.2:c.1194G>A
NM_001754.4:c.1275G>A
NM_001001890.3:c.1194G>A
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 24
BS2 BS4 BS3 BS1 BP2 BP1 BP3 BP5 PS4 PS2 PS3 PS1 BA1 PVS1 PP1 PP3 PP2 PP4 PM3 PM5 PM1 PM4 PM6 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The c.1275G>A (p.Pro425=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing (BP4); in addition, an evolutionary conservation algorithm predicts the site as being non-conserved (PhyloP score = -1.62676 in GRCh38), and the variant allele is the reference nucleotide in one primate and/or three mammal species (BP7). The variant 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 and BP7.
Met criteria codes
BP4
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
BP7
The c.1275G>A (p.Pro425=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, an evolutionary conservation algorithm predicts the site as being non-conserved (PhyloP score = -1.62676 in GRCh38), and the variant allele is the reference nucleotide in one primate and/or three mammal species.
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
gnomAD (v2): ALL: 0.0006959% (1/143694) - NFE: 0.001824% (1/54828) gnomAD (v3): ALL: 0.002008% (3/149438) - NFE: 0.004460% (3/67262)
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
Not applicable
BP3
Not applicable
BP5
Not applicable
PS4
The germline variant has not been reported in cases (LOVD, HGMD, ClinVar, Mastermind, and Google/Google Scholar), but the somatic variant has been detected in a breast and endometrial tumor (COSMIC Genomic Mutation ID: COSV55867658).
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.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
gnomAD (v2): ALL: 0.0006959% (1/143694) - NFE: 0.001824% (1/54828) gnomAD (v3): ALL: 0.002008% (3/149438) - NFE: 0.004460% (3/67262)
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PP3
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
PP2
Not applicable
PP4
Not applicable
PM3
Not applicable
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
PM6
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PM2
gnomAD (v2): ALL: 0.0006959% (1/143694) - NFE: 0.001824% (1/54828) gnomAD (v3): ALL: 0.002008% (3/149438) - NFE: 0.004460% (3/67262)
Curation History
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