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.270G>A (p.Val90=)

CA512318868

1116571 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 142360ab-0f52-479d-abb9-f98ecafaa7aa

HGVS expressions

NM_001754.5:c.270G>A

NM_001754.5(RUNX1):c.270G>A (p.Val90=)

NC_000021.9:g.34886924C>T

CM000683.2:g.34886924C>T

NC_000021.8:g.36259221C>T

CM000683.1:g.36259221C>T

NC_000021.7:g.35181091C>T

NG_011402.2:g.1102788G>A

ENST00000675419.1:c.270G>A

ENST00000300305.7:c.270G>A

ENST00000344691.8:c.189G>A

ENST00000358356.9:c.189G>A

ENST00000399237.6:c.234G>A

ENST00000399240.5:c.189G>A

ENST00000437180.5:c.270G>A

ENST00000455571.5:c.231G>A

ENST00000482318.5:c.59-6211G>A

NM_001001890.2:c.189G>A

NM_001122607.1:c.189G>A

NM_001754.4:c.270G>A

NM_001001890.3:c.189G>A

NM_001122607.2:c.189G>A

Uncertain Significance

PM2_Supporting BP7

PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 PVS1 BA1 BS4 BS3 BS1 BS2 PM5 PM1 PM3 PM4 PM6 BP5 BP2 BP3 BP4 BP1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.270G>A (p.Val90=) is a synonymous variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). Evolutionary conservation prediction algorithms predict the site as not being conserved (phyloP 0.84969 is <2.0) (BP7). 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: PM2_supporting and BP7.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (phyloP 0.84969 is <2.0)

PS4

prevalence of variant is not significantly increased compared to prevalence in controls

PS2

no case studies found

PS1

Amino acid location has not been previously established as pathogenic

PS3

No functional studies found

PP1

no case studies found

PP4

This rule is not applicable for the MM-VCEP

PP3

Synonymous variant therefore no REVEL score applicable and SpliceAI is not ≥0.38 (0.26 Donor Gain)

PP2

This rule is not applicable for the MM-VCEP

PVS1

Not a null variant

BA1

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

BS4

No case studies found

BS3

No functional studies found

BS1

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

BS2

This rule is not applicable for the MM-VCEP

PM5

Not a missense variant

PM1

Not a missense variant

PM3

This rule is not applicable for the MM-VCEP

PM4

Not an in-frame deletion/insertion

PM6

No case studies found

BP5

This rule is not applicable for the MM-VCEP

BP2

Variant absent in gnomAD therefore no homozygotes present

BP3

This rule is not applicable for the MM-VCEP

BP4

Synonymous variant therefore no REVEL score applicable and SpliceAI is not ≤0.20 (0.26 Donor Gain)

BP1

This rule is not applicable for the MM-VCEP

Approved on: 2022-07-08

Published on: 2022-07-08

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