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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.351+6G>T

CA10014547

1001138 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a9d432c7-8944-40a1-9185-2d9cab9a68b4
Approved on: 2023-11-13
Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.351+6G>T
NM_001754.5(RUNX1):c.351+6G>T
NC_000021.9:g.34886837C>A
CM000683.2:g.34886837C>A
NC_000021.8:g.36259134C>A
CM000683.1:g.36259134C>A
NC_000021.7:g.35181004C>A
NG_011402.2:g.1102875G>T
ENST00000675419.1:c.351+6G>T
ENST00000300305.7:c.351+6G>T
ENST00000344691.8:c.270+6G>T
ENST00000358356.9:c.270+6G>T
ENST00000399237.6:c.315+6G>T
ENST00000399240.5:c.270+6G>T
ENST00000437180.5:c.351+6G>T
ENST00000455571.5:c.312+6G>T
ENST00000482318.5:c.59-6124G>T
NM_001001890.2:c.270+6G>T
NM_001122607.1:c.270+6G>T
NM_001754.4:c.351+6G>T
NM_001001890.3:c.270+6G>T
NM_001122607.2:c.270+6G>T

Likely Benign

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The c.351+6G>T variant in RUNX1 is an intronic variant located at a non-conserved nucleotide in intron 4 of NM_001754.5 (BP7); the variant is also known as c.270+6G>T in intron 1 of NM_001001890.3. The results from the in silico splicing predictor SpliceAI supports that this variant does not affect splicing (BP4). The highest population minor allele frequency in gnomAD v2 is 0.01241% (2/16122 alleles) and in gnomAD v3 is 0.009646% (4/41466 alleles) in the African/African American population, and the germline variant has not been reported in patients with the RUNX1-defined phenotype. In summary, this variant meets the criteria to be classified as likely benign for autosomal dominant 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 non-conserved per an evolutionary conservation algorithm (PhyloP score = -0.824843 in GRCh38).
BP4
SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
Not Met criteria codes
PS4
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS2
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
PS3
No relevant data found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Not applicable
PP1
No relevant cases found in literature search, including 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
PM6
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PM2
- gnomAD (v2): ALL: 0.0008053% (2/248360) - AFR: 0.01241% (2/16122) - gnomAD (v3): ALL: 0.002627% (4/152252) - AFR: 0.009646% (4/41466)
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
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Not applicable
BA1
- gnomAD (v2): ALL: 0.0008053% (2/248360) - AFR: 0.01241% (2/16122) - gnomAD (v3): ALL: 0.002627% (4/152252) - AFR: 0.009646% (4/41466)
BS4
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS3
No relevant data found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS1
- gnomAD (v2): ALL: 0.0008053% (2/248360) - AFR: 0.01241% (2/16122) - gnomAD (v3): ALL: 0.002627% (4/152252) - AFR: 0.009646% (4/41466)
BS2
Not applicable
BP5
Not applicable
BP3
Not applicable
BP1
Not applicable
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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