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.1160G>C (p.Gly387Ala)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA410147917

532662 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 796f47f4-6c31-4833-8a66-03f0dc55514a

Approved on: 2025-02-24

Published on: 2025-02-24

HGVS expressions

NM_001754.5:c.1160G>C

NM_001754.5(RUNX1):c.1160G>C (p.Gly387Ala)

NC_000021.9:g.34792418C>G

CM000683.2:g.34792418C>G

NC_000021.8:g.36164715C>G

CM000683.1:g.36164715C>G

NC_000021.7:g.35086585C>G

NG_011402.2:g.1197294G>C

ENST00000675419.1:c.1160G>C

ENST00000300305.7:c.1160G>C

ENST00000344691.8:c.1079G>C

ENST00000399240.5:c.887G>C

ENST00000437180.5:c.1160G>C

ENST00000482318.5:c.*750G>C

NM_001001890.2:c.1079G>C

NM_001754.4:c.1160G>C

NM_001001890.3:c.1079G>C

Uncertain Significance

PS4_Supporting BP4

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

Evidence Links 1

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

The NM_001754.4:c.1160G>C (p.Gly387Ala) variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 27210295). This missense variant has a REVEL score <0.15 (0.141) and SSF and MES predict either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created (BP4). This variant is present at a MAF of 0.000001727 (0.0001727%) in gnomADv4.1.0. In summary, the clinical significance of this variant is uncertain (VUS). ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PS4_ supporting, BP4.

PS4_Supporting

1 Proband

Germline variant (46.3%) in 55 yr old male with myeloid neoplasm along with eosinophilia and FGFR1 gene rearrangement and a somatic R201* variant. Brother poor SCT mobilizer with same germline G387A variant, not counted. PubMed:27210295

BP4

This missense variant has a REVEL score < 0.50 (0.14) and a SpliceAI score ≤ 0.20 (0.0) (BP4).

PP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP2

This rule is not applicable for MM-VCEP

PP3

This missense variant does not have a REVEL score of ≥ 0.88.

PP4

This rule is not applicable for MM-VCEP

PM6

No case study found

PM2

This variant is present at a MAF of 0.000001727 (0.0001727%), present in 2/1158032 alleles in the European (non-Finnish) population of gnomADv.4.1.0

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

PS2

No case study found

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BA1

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

PM1

This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.

PM3

This rule is not applicable for MM-VCEP

PM5

There has not yet been a different missense change determined to be pathogenic at this amino acid residue.

PM4

This variant is not an in-frame deletion/insertion.

PVS1

This variant is not a null variant.

BP5

This rule is not applicable for MM-VCEP

BP7

This variant is not a synonymous or intronic variant.

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

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

BS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS2

This rule is not applicable for MM-VCEP

Curation History

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