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Variant: NM_001754.5(RUNX1):c.247dup (p.Ala83fs)

CA2499225883

1073907 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: a17cc2cb-3b5c-4d98-8710-4f50cc98af79

HGVS expressions

NM_001754.5:c.247dup
NM_001754.5(RUNX1):c.247dup (p.Ala83fs)
NC_000021.9:g.34886948dup
CM000683.2:g.34886948dup
NC_000021.8:g.36259245dup
CM000683.1:g.36259245dup
NC_000021.7:g.35181115dup
NG_011402.2:g.1102765dup
ENST00000675419.1:c.247dup
ENST00000300305.7:c.247dup
ENST00000344691.8:c.166dup
ENST00000358356.9:c.166dup
ENST00000399237.6:c.211dup
ENST00000399240.5:c.166dup
ENST00000437180.5:c.247dup
ENST00000455571.5:c.208dup
ENST00000482318.5:c.59-6234dup
NM_001001890.2:c.166dup
NM_001122607.1:c.166dup
NM_001754.4:c.247dup
NM_001001890.3:c.166dup
NM_001122607.2:c.166dup

Pathogenic

Met criteria codes 3
PVS1 PM2_Supporting PM5_Supporting
Not Met criteria codes 23
PP1 PP4 PP3 PP2 BA1 PM6 PM1 PM4 PM3 BS2 BS1 BS4 BS3 BP7 BP5 BP3 BP2 BP4 BP1 PS2 PS4 PS3 PS1

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.247dup (p.Ala83GlyfsTer?) is an insertion frameshift variant which results in a termination sequence 55 residues later. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant is a nonsense/frameshift variants that is downstream of c.98. This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (+) c.98-c.779 as per VCEP specifications) (PVS1). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting.
Met criteria codes
PVS1
This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (+) c.98-c.779 as per VCEP specifications) (PVS1).
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).
PM5_Supporting
This variant is a nonsense/frameshift variants that is downstream of c.98.
Not Met criteria codes
PP1
Segregation data for this variant has not been reported in literature.
PP4
This rule is not applicable for MM-VCEP.
PP3
This variant does not have applicable in-silico data available.
PP2
This rule is not applicable for MM-VCEP.
BA1
This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.
PM6
De novo data for this variant has not been reported in literature.
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.
PM3
This rule is not applicable for MM-VCEP.
BS2
This rule is not applicable for MM-VCEP.
BS1
This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.
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.
BP7
This variant is not a synonymous or intronic variant.
BP5
This rule is not applicable for MM-VCEP.
BP3
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.
BP4
This variant does not have applicable in-silico data available.
BP1
This rule is not applicable for MM-VCEP.
PS2
De novo data for this variant has not been reported in literature.
PS4
Proband data for this variant has not been reported in literature.
PS3
In vitro or in vivo functional data has not been reported for this variant in the literature.
PS1
There has not yet been a missense change determined to be pathogenic at this amino acid residue.
Approved on: 2023-12-09
Published on: 2023-12-09
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