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.1396A>T (p.Met466Leu)

CA10014176

463982 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2b0ab3a2-cbe9-4769-81a9-29dc6192cfb1
Approved on: 2021-01-11
Published on: 2021-01-11

HGVS expressions

NM_001754.4:c.1396A>T
NM_001754.4(RUNX1):c.1396A>T (p.Met466Leu)
NM_001001890.2:c.1315A>T
NM_001001890.3:c.1315A>T
NM_001754.5:c.1396A>T
ENST00000300305.7:c.1396A>T
ENST00000344691.8:c.1315A>T
ENST00000399240.5:c.1123A>T
ENST00000437180.5:c.1396A>T
ENST00000482318.5:c.*986A>T
NC_000021.9:g.34792182T>A
CM000683.2:g.34792182T>A
NC_000021.8:g.36164479T>A
CM000683.1:g.36164479T>A
NC_000021.7:g.35086349T>A
NG_011402.2:g.1197530A>T
More

Benign

Met criteria codes 2
BA1 BP4
Not Met criteria codes 16
PM5 PM4 PM1 PM2 PM6 PVS1 BS1 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.1396A>T variant that results in a Met466Leu missense change has an MAF of 0.001761 (0.1%, 23/13058 alleles) in the East Asian subpopulation of the gnomAD v2.1.1 cohort, which is >0.0015 (0.15%) (BA1). This missense variant has a REVEL score <0.15 (0.149) and SSF and MES predict no effect on splicing (BP4). The variant has not been reported in the germ line of 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 benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4.
Met criteria codes
BA1
The variant is reported at a frequency of 0.001761 (23/13058 East Asian alleles) in gnomAD v2.1.1 and a frequency of 0.0006447 (2/3102 East Asian alleles) in gnomAD v3. The gnomAD v2 frequency meets criteria for BA1; threshold: >0.0015.
BP4
The REVEL score for this missense variant is 0.149 and SSF/MES predict no effect on splicing. The variant meets criteria for BP4.
Not Met criteria codes
PM5
No data currently available
PM4
N/A
PM1
N/A
PM2
Meets BA1
PM6
No data currently available
PVS1
N/A
BS1
Meets BA1
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 the germ line of 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
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.