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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001754.5(RUNX1):c.1317C>T (p.Ser439=)

CA16616504

415831 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2c4f9e62-f097-4573-acc3-06b1eecaf9f0
Approved on: 2024-08-28
Published on: 2024-08-28

HGVS expressions

NM_001754.5:c.1317C>T
NM_001754.5(RUNX1):c.1317C>T (p.Ser439=)
NC_000021.9:g.34792261G>A
CM000683.2:g.34792261G>A
NC_000021.8:g.36164558G>A
CM000683.1:g.36164558G>A
NC_000021.7:g.35086428G>A
NG_011402.2:g.1197451C>T
ENST00000675419.1:c.1317C>T
ENST00000300305.7:c.1317C>T
ENST00000344691.8:c.1236C>T
ENST00000399240.5:c.1044C>T
ENST00000437180.5:c.1317C>T
ENST00000482318.5:c.*907C>T
NM_001001890.2:c.1236C>T
NM_001754.4:c.1317C>T
NM_001001890.3:c.1236C>T
More

Likely Benign

Met criteria codes 3
PM2_Supporting BP7 BP4
Not Met criteria codes 23
PS4 PS2 PS1 PS3 BA1 PP4 PP1 PP3 PP2 PM6 PM3 PM5 PM1 PM4 PVS1 BS4 BS3 BS1 BS2 BP5 BP2 BP3 BP1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.1317C>T (p.Ser439=) is a synonymous variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). The 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. Additionally, evolutionary conservation algorithms predict the site as not being highly conserved (PhyloP score: -0.44 < 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, BP7, PM2_supporting.
Met criteria codes
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).
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: -0.44 < 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 (BP4).
Not Met criteria codes
PS4
Proband data for this variant has not been reported in literature.
PS2
De novo data for this variant has not been reported in literature.
PS1
There has not yet been a missense change determined to be pathogenic at this amino acid residue.
PS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
BA1
This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
PP4
This rule is not applicable for MM-VCEP.
PP1
Segregation data for this variant has not been reported in literature.
PP3
This synonymous or intronic variant does not have a REVEL score ≥ 0.88 or a SpliceAI score ≥ 0.38.
PP2
This rule is not applicable for MM-VCEP.
PM6
De novo data for this variant has not been reported in literature.
PM3
This rule is not applicable for MM-VCEP.
PM5
There has not yet been a different missense change determined to be pathogenic at this amino acid residue.
PM1
This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.
PM4
This variant is not an in-frame deletion/insertion.
PVS1
This variant is not a null variant.
BS4
Segregation data for this variant has not been reported in literature.
BS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
BS1
This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.
BS2
This rule is not applicable for MM-VCEP.
BP5
This rule is not applicable for MM-VCEP.
BP2
This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
BP3
This rule is not applicable for MM-VCEP.
BP1
This rule is not applicable for MM-VCEP.
Curation History
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