The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]


Variant: NM_001754.4(RUNX1):c.787C>T (p.Pro263Ser)

CA10014358

464008 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 6008d288-a114-40c0-b768-5f36eaaecb6c
Approved on: 2022-07-08
Published on: 2022-07-08

HGVS expressions

NM_001754.4:c.787C>T
NM_001754.4(RUNX1):c.787C>T (p.Pro263Ser)
NC_000021.9:g.34834428G>A
CM000683.2:g.34834428G>A
NC_000021.8:g.36206725G>A
CM000683.1:g.36206725G>A
NC_000021.7:g.35128595G>A
NG_011402.2:g.1155284C>T
ENST00000675419.1:c.787C>T
ENST00000300305.7:c.787C>T
ENST00000344691.8:c.706C>T
ENST00000358356.9:c.706C>T
ENST00000399237.6:c.751C>T
ENST00000399240.5:c.532+25046C>T
ENST00000437180.5:c.787C>T
ENST00000469087.1:n.323C>T
ENST00000482318.5:c.*377C>T
NM_001001890.2:c.706C>T
NM_001122607.1:c.706C>T
NM_001001890.3:c.706C>T
NM_001122607.2:c.706C>T
NM_001754.5:c.787C>T
NM_001754.5(RUNX1):c.787C>T (p.Pro263Ser)
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Uncertain Significance

The Expert Panel has overridden the computationally generated classification - "[unknown]"
Not Met criteria codes 26
PVS1 BS3 BS4 BS1 BS2 BP7 BP5 BP3 BP2 BP4 BP1 PS1 PS3 PS2 PS4 BA1 PP4 PP1 PP3 PP2 PM4 PM5 PM1 PM3 PM6 PM2

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

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.5(RUNX1):c.787C>T (p.Pro263Ser) variant is reported at a frequency of 0.00004476 (0.004%, 5/111718 alleles) in the non-Finnish European population of gnomAD v2.1.1 cohort which does not fall within 0.00015 (0.015%) and 0.0015 (0.15%) range, thus not meeting BS1 criteria. 1 patient from PMID: 24764152 with chronic myelomonocytic leukemia is reported with the Pro263Ser variant at a VAF of 49%. Patient also had variants in SETBP1 and U2AF1. However, information on germ line confirmation is not available. Proband does not meet criteria for PS4. This missense variant has a REVEL score 0.286, which does not meet criteria for PP3 or BP4. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: none.
Not Met criteria codes
PVS1
N/A
BS3
No data currently available
BS4
No data currently available
BS1
MAF of 0.00004476 (0.004%, 5/111718 alleles) in the non-Finnish European population of gnomAD v2.1.1 cohort which does not fall within 0.00015 (0.015%) and 0.0015 (0.15%). BS1 criteria not met.
BS2
MM-VCEP deemed N/A for RUNX1
BP7
N/A
BP5
MM-VCEP deemed N/A for RUNX1
BP3
MM-VCEP deemed N/A for RUNX1
BP2
No evidence
BP4
This missense variant DOES NOT have a REVEL score <0.15 (0.286). SpliceAI predicts loss of donor splice site of intron 6 with a score of 0.03.
BP1
MM-VCEP deemed N/A for RUNX1
PS1
No data currently available
PS3
No data currently available
PS2
No data currently available
PS4
1 patient from PMID: 24764152 with chronic myelomonocytic leukemia is reported with the Pro263Ser variant at a VAF of 49%. Patient also had variants in SETBP1 and U2AF1. However, information on germ line confirmation is not available. Proband does not meet criteria for PS4.
BA1
N/A
PP4
MM-VCEP deemed N/A for RUNX1
PP1
No data currently available
PP3
This missense variant DOES NOT have a REVEL score >0.75 (0.286)
PP2
MM-VCEP deemed N/A for RUNX1
PM4
N/A
PM5
No data currently available
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
MM-VCEP deemed N/A for RUNX1
PM6
No data currently available
PM2
Variant reported in gnomAD
Curation History
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