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.496C>A (p.Arg166=)

CA10014502

570036 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 78d5219e-fd6a-41aa-ad83-9dcf935a1544

HGVS expressions

NM_001754.5:c.496C>A

NM_001754.5(RUNX1):c.496C>A (p.Arg166=)

NC_000021.9:g.34880569G>T

CM000683.2:g.34880569G>T

NC_000021.8:g.36252866G>T

CM000683.1:g.36252866G>T

NC_000021.7:g.35174736G>T

NG_011402.2:g.1109143C>A

ENST00000675419.1:c.496C>A

ENST00000300305.7:c.496C>A

ENST00000344691.8:c.415C>A

ENST00000358356.9:c.415C>A

ENST00000399237.6:c.460C>A

ENST00000399240.5:c.415C>A

ENST00000437180.5:c.496C>A

ENST00000482318.5:c.*86C>A

NM_001001890.2:c.415C>A

NM_001122607.1:c.415C>A

NM_001754.4:c.496C>A

NM_001001890.3:c.415C>A

NM_001122607.2:c.415C>A

Likely Benign

BP4 BP7

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

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.496C>A (p.Arg166=) is a synonymous variant. Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.6 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). Synonymous variant therefore no REVEL score and SpliceAI is ≤ 0.20 (0.14) (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7.

BP4

Synonymous variant therefore no REVEL score and SpliceAI is ≤ 0.20 (0.14) (BP4)

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.6 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

PM6

nil data

PM2

AF 3.98e-6 gnomAD V2

PM3

not applicable

PM4

synonymous variant

PM1

Not a missense variant

PM5

No known established pathogenic variants at this codon

PVS1

synonymous variant not involving splice site

BS2

not applicable

BS4

nil data

BS3

nil data

BS1

AF 3.98e-6 gnomAD V2

BP2

not applicable

BP3

synonymous variant

BP1

not applicable

BP5

not applicable

PS2

nil data

PS4

nil data

PS3

nil data

PS1

No known established pathogenic variants at this codon

BA1

AF 3.98e-6 gnomAD V2

PP4

not applicable

PP1

nil data

PP3

Synonymous variant therefore no REVEL score and SpliceAI is not ≥0.38 (0.14)

PP2

not applicable

Approved on: 2022-08-23

Published on: 2023-11-13

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