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.613+20G>T

CA10014471

1965125 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1f135cb7-3a71-4be4-8f6a-5f867fc92f38
Approved on: 2024-09-18
Published on: 2024-09-18

HGVS expressions

NM_001754.5:c.613+20G>T
NM_001754.5(RUNX1):c.613+20G>T
NC_000021.9:g.34859454C>A
CM000683.2:g.34859454C>A
NC_000021.8:g.36231751C>A
CM000683.1:g.36231751C>A
NC_000021.7:g.35153621C>A
NG_011402.2:g.1130258G>T
ENST00000675419.1:c.613+20G>T
ENST00000300305.7:c.613+20G>T
ENST00000344691.8:c.532+20G>T
ENST00000358356.9:c.532+20G>T
ENST00000399237.6:c.577+20G>T
ENST00000399240.5:c.532+20G>T
ENST00000437180.5:c.613+20G>T
ENST00000467577.1:n.105+20G>T
ENST00000482318.5:c.*203+20G>T
NM_001001890.2:c.532+20G>T
NM_001122607.1:c.532+20G>T
NM_001754.4:c.613+20G>T
NM_001001890.3:c.532+20G>T
NM_001122607.2:c.532+20G>T
More

Likely Benign

Met criteria codes 2
BP7 BP4
Not Met criteria codes 15
BS3 BS1 BS2 PP3 PP2 PP4 PM2 PM5 PM3 PS3 PS4 PS1 BA1 BP1 BP2

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.613+20G>T is an intronic variant which is not predicted by SpliceAI to impact splicing (BP4). Additionally, an evolutionary conservation algorithm predicts the site as not being highly conserved (PhyloP score = 1.29065 in GRCh38) (BP7). The highest population minor allele frequency in gnomAD v2 and v4 is 0.00002891 (1/34,590 alleles) and 0.00002241 (1/44,630 alleles), respectively, in the admixed American population. This variant has not been reported in 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
BP7
This intronic variant is located at a nucleotide that is not highly conserved per an evolutionary conservation algorithm (PhyloP score = 1.29065 in GRCh38).
BP4
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
Not Met criteria codes
BS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS1
gnomAD v2: ALL: 0.0003977% (1/251444) - AMR: 0.002891% (1/34590) gnomAD v3: Absent with ~30x coverage gnomAD v4: ALL: 0.00007201% (1/1388602) - AMR: 0.002241% (1/44630)
BS2
Not applicable
PP3
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
PP2
Not applicable
PP4
Not applicable
PM2
gnomAD v2: ALL: 0.0003977% (1/251444) - AMR: 0.002891% (1/34590) gnomAD v3: Absent with ~30x coverage gnomAD v4: ALL: 0.00007201% (1/1388602) - AMR: 0.002241% (1/44630)
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Not applicable
PS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS4
No relevant cases found in literature search, including 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: 0.0003977% (1/251444) - AMR: 0.002891% (1/34590) gnomAD v3: Absent with ~30x coverage gnomAD v4: ALL: 0.00007201% (1/1388602) - AMR: 0.002241% (1/44630)
BP1
Not applicable
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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