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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001754.5(RUNX1):c.317G>A (p.Trp106Ter)

CA410203506

988835 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 4f2f5136-8a82-4077-9cf2-6ddf6f2a0efc

HGVS expressions

NM_001754.5:c.317G>A

NM_001754.5(RUNX1):c.317G>A (p.Trp106Ter)

NC_000021.9:g.34886877C>T

CM000683.2:g.34886877C>T

NC_000021.8:g.36259174C>T

CM000683.1:g.36259174C>T

NC_000021.7:g.35181044C>T

NG_011402.2:g.1102835G>A

ENST00000675419.1:c.317G>A

ENST00000300305.7:c.317G>A

ENST00000344691.8:c.236G>A

ENST00000358356.9:c.236G>A

ENST00000399237.6:c.281G>A

ENST00000399240.5:c.236G>A

ENST00000437180.5:c.317G>A

ENST00000455571.5:c.278G>A

ENST00000482318.5:c.59-6164G>A

NM_001001890.2:c.236G>A

NM_001122607.1:c.236G>A

NM_001754.4:c.317G>A

NM_001001890.3:c.236G>A

NM_001122607.2:c.236G>A

Pathogenic

PS4_Supporting PVS1 PM2_Supporting

PS2 PS3 PS1 PP1 PP4 PP3 PP2 PM1 PM5 PM3 PM4 PM6 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP7 BP5

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The NM_001754.5(RUNX1):c.317G>A (p.Trp106Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). The variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_Supporting; PMID: 24100448). 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 and PS4_Supporting.

PS4_Supporting

The variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 24100448).

PVS1

The NM_001754.5(RUNX1):c.317G>A (p.Trp106Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1)

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

PS2

N/A

PS3

N/A

PS1

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

PP1

Evidence not found

PP4

This rule is not applicable for MM-VCEP

PP3

Nonsense variant therefore PP3 is not met

PP2

This rule is not applicable for MM-VCEP

PM1

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

PM5

Nonsense variant.

PM3

This rule is not applicable for MM-VCEP

PM4

Nonsense variant

PM6

N/A

BA1

No population data was found for this allele in gnomAD Version 2.1.1.

BS2

This rule is not applicable for MM-VCEP

BS4

Evidence not found

BS3

N/A

BS1

No population data was found for this allele in gnomAD Version 2.1.1.

BP2

Evidence not found

BP3

This rule is not applicable for MM-VCEP

BP4

Nonsense variant therefore BP4 is not met

BP1

This rule is not applicable for MM-VCEP

BP7

Nonsense variant, therefore BP7 is not met.

BP5

This rule is not applicable for MM-VCEP

Approved on: 2022-01-20

Published on: 2022-06-23

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