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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.219C>T (p.Ser73=)

CA512318910

532675 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: f328f465-a8c2-4bc8-baee-39f4c9263b8a

HGVS expressions

NM_001754.4:c.219C>T
NM_001754.4(RUNX1):c.219C>T (p.Ser73=)
NM_001001890.2:c.138C>T
NM_001122607.1:c.138C>T
NM_001001890.3:c.138C>T
NM_001122607.2:c.138C>T
ENST00000300305.7:c.219C>T
ENST00000344691.8:c.138C>T
ENST00000358356.9:c.138C>T
ENST00000399237.6:c.183C>T
ENST00000399240.5:c.138C>T
ENST00000437180.5:c.219C>T
ENST00000455571.5:c.180C>T
ENST00000482318.5:c.59-6262C>T
NC_000021.9:g.34886975G>A
CM000683.2:g.34886975G>A
NC_000021.8:g.36259272G>A
CM000683.1:g.36259272G>A
NC_000021.7:g.35181142G>A
NG_011402.2:g.1102737C>T

Likely Benign

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

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created; in addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score 0.04 < 0.1[-14.1;6.4]) (BP4+BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and BP7.
Met criteria codes
BP7
This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created. In addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score 0.04 < 0.1 [-14.1;6.4]).
BP4
This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created.
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
ALL:0.00042% (1/239124 alleles) - AMR:0.0029% (1/34042 alleles) (gnomAD v2) Not present in gnomAD v3
BS1
ALL:0.00042% (1/239124 alleles) - AMR:0.0029% (1/34042 alleles) (gnomAD v2) Not present in gnomAD v3
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
Not applicable
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 105-204.
PM2
ALL:0.00042% (1/239124 alleles) - AMR:0.0029% (1/34042 alleles) (gnomAD v2) Not present in gnomAD v3
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2020-04-10
Published on: 2020-06-02
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