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
ENST00000675419.1:c.985G>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
NM_001001890.2:c.904G>A
NM_001001890.3:c.904G>A
NM_001754.5:c.985G>A
More

Likely Benign

Met criteria codes 2
BP4 BS1
Not Met criteria codes 24
PP1 PP2 PP3 PP4 PM6 PM2 PM1 PM3 PM5 PM4 PS1 PS2 PS3 PS4 BA1 PVS1 BP3 BP1 BP2 BP5 BP7 BS2 BS4 BS3

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
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.
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.
Not Met criteria codes
PP1
No data currently available
PP2
MM-VCEP deemed N/A for RUNX1
PP3
Meets BP4
PP4
MM-VCEP deemed N/A for RUNX1
PM6
No data currently available
PM2
Meets BS1
PM1
N/A
PM3
MM-VCEP deemed N/A for RUNX1
PM5
No data currently available
PM4
N/A
PS1
No data currently available
PS2
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
BA1
Meets BS1
PVS1
N/A
BP3
MM-VCEP deemed N/A for RUNX1
BP1
MM-VCEP deemed N/A for RUNX1
BP2
N/A
BP5
MM-VCEP deemed N/A for RUNX1
BP7
N/A
BS2
MM-VCEP deemed N/A for RUNX1
BS4
No data currently available
BS3
No data currently available
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.