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.445G>A (p.Ala149Thr)

CA10014513

532652 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 1d8db461-fa99-4edb-b003-78869936b6d9

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.445G>A

NM_001754.5(RUNX1):c.445G>A (p.Ala149Thr)

NC_000021.9:g.34880620C>T

CM000683.2:g.34880620C>T

NC_000021.8:g.36252917C>T

CM000683.1:g.36252917C>T

NC_000021.7:g.35174787C>T

NG_011402.2:g.1109092G>A

ENST00000675419.1:c.445G>A

ENST00000300305.7:c.445G>A

ENST00000344691.8:c.364G>A

ENST00000358356.9:c.364G>A

ENST00000399237.6:c.409G>A

ENST00000399240.5:c.364G>A

ENST00000437180.5:c.445G>A

ENST00000455571.5:c.406G>A

ENST00000482318.5:c.*35G>A

NM_001001890.2:c.364G>A

NM_001122607.1:c.364G>A

NM_001754.4:c.445G>A

NM_001001890.3:c.364G>A

NM_001122607.2:c.364G>A

Uncertain Significance

PM1_Supporting

BS2 BS4 BS3 BS1 PVS1 PS1 PS2 PS4 PS3 BP2 BP3 BP4 BP1 BP7 BP5 BA1 PP1 PP4 PP3 PP2 PM5 PM3 PM4 PM6 PM2

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.445G>A (p.Ala149Thr) is a missense variant which is located within the Runt Homology Domain (AA 89-204), but does not occur in an established hotspot residue (PM1_supporting). 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: PM1_supporting.

PM1_Supporting

This missense variant occurs at residue 149 which is located within the Runt Homology Domain (AA 89-204), but does not occur in an established hotspot residue (PM1_supporting).

BS2

This rule is not applicable for MM.VCEP.

BS4

There is no evidence available.

BS3

There are no functional studies that have incorporated this variant.

BS1

This variant has been found at a very low frequency (0.00001470) in gnomAD v3.1.2 and is absent in gnomAD v2.1.1.

PVS1

This is a missense variant.

PS1

Not reported.

PS2

There is no evidence available.

PS4

There is no evidence available.

PS3

There are no functional studies that have incorporated this variant.

BP2

There is no evidence available.

BP3

This rule is not applicable for MM.VCEP.

BP4

The REVEL score = 0.767 which is above the threshold for a benign variant (0.5). The Splice AI score =0 which is below the threshold of risk for a splicing defect (<0.2).

BP1

This rule is not applicable for MM.VCEP.

BP7

This is a missense variant.

BP5

This rule is not applicable for MM.VCEP.

BA1

This variant has been found at a very low frequency (0.00001470) in gnomAD v3.1.2 and is absent in gnomAD v2.1.1.

PP1

There is no evidence available.

PP4

This rule is not applicable for MM.VCEP.

PP3

The REVEL score = 0.767 which is below the threshold for pathogenicity (0.88). The Splice AI score =0 which is below the threshold for a splicing defect (0.38).

PP2

This rule is not applicable for MM.VCEP.

PM5

No other missense changes reported in Clinvar at this site.

PM3

This rule is not applicable for MM.VCEP.

PM4

This is a missense variant.

PM6

There is no evidence available.

PM2

This variant has been found at a very low frequency (0.00001470) in gnomAD v3.1.2 and is absent in gnomAD v2.1.1.

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