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.985G>A (p.Ala329Thr)

CA410148791

464015 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2967f0b8-1610-443c-bd6e-82e925e748ed
Approved on: 2020-05-13
Published on: 2020-06-02

HGVS expressions

NM_001754.4:c.985G>A
NM_001754.4(RUNX1):c.985G>A (p.Ala329Thr)
NC_000021.9:g.34792593C>T
CM000683.2:g.34792593C>T
NC_000021.8:g.36164890C>T
CM000683.1:g.36164890C>T
NC_000021.7:g.35086760C>T
NG_011402.2:g.1197119G>A
NM_001001890.2:c.904G>A
NM_001001890.3:c.904G>A
ENST00000300305.7:c.985G>A
ENST00000344691.8:c.904G>A
ENST00000399240.5:c.712G>A
ENST00000437180.5:c.985G>A
ENST00000482318.5:c.*575G>A
More

Likely Benign

Met criteria codes 2
BS1 BP4
Not Met criteria codes 16
PM5 PM4 PM1 PM2 PM6 PVS1 BA1 BS3 BS4 BP2 BP7 PS1 PS3 PS4 PP3 PP1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.4:c.985G>A variant that results in a Ala329Thr missense change has an MAF of 0.0002825 (0.02%, 9/21854 alleles) in the Latino subpopulation of the gnomAD v2.1.1 cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This missense variant has a REVEL score <0.15 (0.067) and splicing tools predict no splicing impact (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, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BP4.
Met criteria codes
BS1
The variant is reported in gnomAD v2.1.1 at a frequency of 0.0002825 (9/31854 Latino alleles) and in gnomAD v3 at a frequency of 0.0002198 (3/13650 Latino alleles) with 0 homozygotes. The gnomAD v2 population frequency meets criteria to apply BS1 for this variant.
BP4
The variant has a REVEL score of 0.067, threshold: <0.15. SSF & MES predict no splicing impact. MES suggests creation of cryptic splice sites; however, SSF does not concur. Therefore, BP4 is met.
Not Met criteria codes
PM5
No data currently available
PM4
N/A
PM1
N/A
PM2
Meets BS1
PM6
No data currently available
PVS1
N/A
BA1
Meets BS1
BS3
No data currently available
BS4
No data currently available
BP2
N/A
BP7
N/A
PS1
No data currently available
PS3
No data currently available
PS4
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
PP3
Meets BP4
PP1
No data currently available
Curation History
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