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.265C>T (p.Leu89=)

CA16616271

415829 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7c5432bb-5dbc-4e42-8f20-7c853194a636

HGVS expressions

NM_001754.5:c.265C>T

NM_001754.5(RUNX1):c.265C>T (p.Leu89=)

NC_000021.9:g.34886929G>A

CM000683.2:g.34886929G>A

NC_000021.8:g.36259226G>A

CM000683.1:g.36259226G>A

NC_000021.7:g.35181096G>A

NG_011402.2:g.1102783C>T

ENST00000675419.1:c.265C>T

ENST00000300305.7:c.265C>T

ENST00000344691.8:c.184C>T

ENST00000358356.9:c.184C>T

ENST00000399237.6:c.229C>T

ENST00000399240.5:c.184C>T

ENST00000437180.5:c.265C>T

ENST00000455571.5:c.226C>T

ENST00000482318.5:c.59-6216C>T

NM_001001890.2:c.184C>T

NM_001122607.1:c.184C>T

NM_001754.4:c.265C>T

NM_001001890.3:c.184C>T

NM_001122607.2:c.184C>T

Uncertain Significance

BP4

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

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.265C>T (p.Leu89=) is a synonymous variant. The SpliceAI score is ≤0.20 (0) (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 is a synonymous variant therefore no REVEL score is applicable and SpliceAI score is ≤0.20 (0) (BP4).

PS1

This is a synonymous variant.

PS2

To our knowledge, no publication has reported this variant to date as de novo.

PS3

To our knowledge, this synonymous variant was not evaluated in transactivation assays.

BA1

This variant is absent from gnomAD v2.1.1 (mean depth coverage > 70 for exam and genome). The highest population minor allele frequency in gnomAD v 3.1.2 is 0.00002412 (1/41452 alleles) in African/African American population.

PP4

This rule is not applicable to the MMVCEP

PP1

There is one (/two?) entry(ies) in Clinvar for this variant but the affected status is unknown (Clinvar ID 415829).

PP3

This is a synonymous variant therefore no REVEL score is applicable and SpliceAI score is < 0.38 (0) (PP3).

PP2

This rule is not applicable to the MMVCEP. (22 benign missense variants vs 27 pathogenic missense variants in RUNX1)

PM5

This is a synonymous variant.

PM3

This rule is not applicable to the MMVCEP

PM1

PM1 cannot be applied because this variant is a synonymous variant.

PM4

PM4 cannot be applied because this variant is a synonymous variant.

PM6

To our knowledge, no publication has reported this variant to date as de novo.

PM2

PVS1

PVS1 cannot be applied because this variant is a synonymous variant.

BS2

This rule is not applicable to the MMVCEP

BS4

There is one (/two?) entry(ies) in Clinvar for this variant but the affected status is unknown (Clinvar ID 415829).

BS3

To our knowledge, this synonymous variant was not evaluated in transactivation assays.

BS1

BP2

To our knowledge, no publication has reported this information to date.

BP3

BP3 cannot be applied because this variant is a synonymous variant.

BP1

This rule is not applicable to the MMVCEP. (27 pathogenic missense variants in clinvar vs 88 pathogenic null variants)

BP5

This rule is not applicable to the MMVCEP

BP7

BP7 was not applied because the nucleotide is conserved, as shown by phyloP100 (6.18).

Approved on: 2023-11-13

Published on: 2023-11-13

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