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]

Variant: NM_001754.5(RUNX1):c.735C>G (p.Pro245=)

CA512318600

1124345 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: 8651b813-3751-40f3-a05a-327304279dd3

Approved on: 2026-04-29

Published on: 2026-04-29

HGVS expressions

NM_001754.5(RUNX1):c.735C>G (p.Pro245=)

NM_001754.5:c.735C>G

NC_000021.9:g.34834480G>C

CM000683.2:g.34834480G>C

NC_000021.8:g.36206777G>C

CM000683.1:g.36206777G>C

NC_000021.7:g.35128647G>C

NG_011402.2:g.1155232C>G

ENST00000675419.1:c.735C>G

ENST00000300305.7:c.735C>G

ENST00000344691.8:c.654C>G

ENST00000358356.9:c.654C>G

ENST00000399237.6:c.699C>G

ENST00000399240.5:c.532+24994C>G

ENST00000437180.5:c.735C>G

ENST00000469087.1:n.271C>G

ENST00000482318.5:c.*325C>G

NM_001001890.2:c.654C>G

NM_001122607.1:c.654C>G

NM_001754.4:c.735C>G

NM_001001890.3:c.654C>G

NM_001122607.2:c.654C>G

Likely Benign

BP4 BP7 PM2_Supporting

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

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 for RUNX1 Version 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.735C>G (p.Pro245=) is a synonymous variant which has a SpliceAI score ≤ 0.20 (0.02) (BP4, BP7). This variant has a MAF ≤ 0.00005 in gnomAD v4 across all subpopulations with at least 20x coverage for RUNX1 (PM2_supporting). 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, PM2_supporting.

BP4

This a synonymous variant. SpliceAI was <0.20 (Donor Loss score of 0.02)

BP7

This a synonymous variant. SpliceAI was <0.20 (Donor Loss score of 0.02)

PM2_Supporting

This variant has a MAF ≤ 0.00005 in gnomAD v4.0 in all subpopulations with at least 20X coverage for RUNX1 (PM2_supporting).

PS2

No other de novo cases with phenotype reported.

PS4

No published cases reported.

PS3

This is a synonymous variant with no functional studies reported.

PS1

This is a synonymous variant.

BP2

Other pathogenic variant not known.

BP1

This rule is not applicable for MM-VCEP.

BP3

This rule is not applicable for MM-VCEP.

BP5

This rule is not applicable for MM-VCEP.

PP1

No segregation data available.

PP3

This is a synonymous variant not located within the last 3 bases of an exon splice donor or splice acceptor site. SpliceAI score is <0.20.

PP2

This rule is not applicable for MM-VCEP.

PP4

This rule is not applicable for MM-VCEP.

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

PM6

No other de novo cases with phenotype reported.

PM1

This is a synonymous variant.

PM5

This is a synonymous variant.

PM3

This rule is not applicable for MM-VCEP.

PM4

This is a synonymous variant.

BS2

This rule is not applicable for MM-VCEP.

BS4

No segregation data available.

BS3

This is a synonymous variant with no functional studies reported.

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

PVS1

This is a synonymous variant.

Curation History

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