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]
  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.998C>G (p.Pro333Arg)

CA410148693

572808 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4e2707eb-f96a-47cd-b129-b2b5449560db
Approved on: 2020-02-14
Published on: 2020-06-02

HGVS expressions

NM_001754.4:c.998C>G
NM_001754.4(RUNX1):c.998C>G (p.Pro333Arg)
NM_001001890.2:c.917C>G
NM_001001890.3:c.917C>G
ENST00000300305.7:c.998C>G
ENST00000344691.8:c.917C>G
ENST00000399240.5:c.725C>G
ENST00000437180.5:c.998C>G
ENST00000482318.5:c.*588C>G
NC_000021.9:g.34792580G>C
CM000683.2:g.34792580G>C
NC_000021.8:g.36164877G>C
CM000683.1:g.36164877G>C
NC_000021.7:g.35086747G>C
NG_011402.2:g.1197132C>G
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Uncertain Significance

Not Met criteria codes 18
PVS1 PS3 PS4 PS1 BA1 PP3 PP1 PM2 PM6 PM4 PM1 PM5 BS1 BS3 BS4 BP7 BP4 BP2

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.4(RUNX1):c.998C>G (p.Pro333Arg) variant is reported in gnomAD at a frequency of 0.0001242 and does not meet any of the population criteria defined by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1. It has a low REVEL score (0.33), and does not meet criteria for PP3or BP4. The variant has not been reported in patients with familial platelet disorder with predisposition to hematologic malignancies in the literature, to the best of our knowledge. 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
PS3
No data currently available
PS4
The variant is reported once in the literature in an individual with chordoma. No reports of this variant seen in patients with Familial platelet disorder with predisposition to hematologic malignancies. From internal laboratory data (SCV000822724.1): Patient does not meet RUNX1 phenotype criteria. However, PS4 may not be applied as 4 allele counts are reported in gnomAD for this variant.
The patient was M/65y with a sacral chordoma that metastasized. Variants detected in this patient (sequencing of FF and FFPE tumor tissues) included ARIDIB p.V602A; RUNXI p.P333R & p.M267I; ASXLI p.T822A; CREBBP p.W1676C; PTPRD p.M1253I PubMed:27072194
PS1
No data currently available
BA1
The variant is reported in gnomAD at a frequency of 0.0001242 (4/32194) Latino alleles, and does not meet criteria for BA1 (AF >0.0015)
PP3
The variant has a REVEL score of 0.33 and does not meet criteria for PP3 (threshold: > 0.75)
PP1
No data currently available
PM2
variant reported in gnomAD
PM6
No data currently available
PM4
N/A
PM1
N/A
PM5
Pro333Leu is a variant seen at the same residue (reported in gnomAD); however, this has not been reported in patients with Familial platelet disorder with predisposition to hematologic malignancies and has yet to be evaluated by MM-VCEP
BS1
The variant is reported in gnomAD at a frequency of 0.0001242 (4/32194) Latino alleles, and does not meet criteria for BS1 (0.0015 > AF > 0.00015)
BS3
No data currently available
BS4
No data currently available
BP7
N/A
BP4
The variant has a REVEL score of 0.33 and does not meet criteria for BP4 (threshold: < 0.15)
BP2
No data currently available
Curation History
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