Submissions for variant NM_001754.5(RUNX1):c.1389C>G (p.Pro463=)

gnomAD frequency: 0.04709  dbSNP: rs61750222

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV000327560	SCV000965632	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2019-08-02	reviewed by expert panel	curation	The MAF for the synonymous variant, NM_001754.4:c.1389C>G (p.Pro463=) is 0.1206 (12%, 1976/16382 alleles) in the African subpopulation of the gnomAD cohort, which is >/= 0.0015 (0.15%) (BA1). This variant is predicted by SSF and MES to lead to 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 (BP4). This synonymous variant is predicted by evolutionary conservation prediction algorithms that the site is not conserved (PhyloP score -0.503315 <0.1) (BP7). This variant is detected in a homozygous state in 202 individuals in a gnomAD (BP2). 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, BP2, BP4, BP7.
PreventionGenetics, part of Exact Sciences	RCV000241802	SCV000308030	benign	not specified	2018-04-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000327560	SCV000435942	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000327560	SCV001731622	benign	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001651159	SCV001870726	benign	not provided	2018-06-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001651159	SCV002047918	benign	not provided	2021-04-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316391	SCV004015354	benign	Acute myeloid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000241802	SCV001798085	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000241802	SCV001932258	benign	not specified		no assertion criteria provided	clinical testing