Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001754.5(RUNX1):c.219C>G (p.Ser73Arg)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410203871

1037898 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e10a769a-393a-4882-a254-3a6736e2a739

Approved on: 2024-11-13

Published on: 2024-11-13

HGVS expressions

NM_001754.5:c.219C>G

NM_001754.5(RUNX1):c.219C>G (p.Ser73Arg)

NC_000021.9:g.34886975G>C

CM000683.2:g.34886975G>C

NC_000021.8:g.36259272G>C

CM000683.1:g.36259272G>C

NC_000021.7:g.35181142G>C

NG_011402.2:g.1102737C>G

ENST00000675419.1:c.219C>G

ENST00000300305.7:c.219C>G

ENST00000344691.8:c.138C>G

ENST00000358356.9:c.138C>G

ENST00000399237.6:c.183C>G

ENST00000399240.5:c.138C>G

ENST00000437180.5:c.219C>G

ENST00000455571.5:c.180C>G

ENST00000482318.5:c.59-6262C>G

NM_001001890.2:c.138C>G

NM_001122607.1:c.138C>G

NM_001754.4:c.219C>G

NM_001001890.3:c.138C>G

NM_001122607.2:c.138C>G

Uncertain Significance

BP4

BA1 BS2 BS1 BS4 BS3 BP3 BP1 BP2 PVS1 BP5 BP7 PS1 PS2 PS3 PS4 PP1 PP2 PP3 PP4 PM6 PM2 PM1 PM3 PM5 PM4

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.219C>G (p.Ser73Arg) is a missense variant which has a REVEL score < 0.50 (0.411) and a SpliceAI score ≤ 0.20 (0.03) (BP4). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4.

BP4

This missense variant has a REVEL score < 0.50 (0.411) and a SpliceAI score ≤ 0.20 (0.03) (BP4).

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

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.

BP3

This rule is not applicable for MM-VCEP.

BP1

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.

PVS1

This variant is not a null variant.

BP5

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

PS2

De novo 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.

PS4

Proband data for this variant has not been reported in literature.

PP1

Segregation data for this variant has not been reported in literature.

PP2

This rule is not applicable for MM-VCEP.

PP3

This missense variant does not have a REVEL score of ≥ 0.88.

PP4

This rule is not applicable for MM-VCEP.

PM6

De novo data for this variant has not been reported in literature.

PM2

This variant is present in at least one population database.

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.

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.

PM4

This variant is not an in-frame deletion/insertion.

Curation History

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