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

UUID: f328f465-a8c2-4bc8-baee-39f4c9263b8a

Approved on: 2020-04-10

Published on: 2020-06-02

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: BP7 BP4

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

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

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
• PVS1: 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
• 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
• 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
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline