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.122C>T (p.Thr41Met)

CA10014590

661459 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 546a3ea3-a27c-46e7-a9a2-463a702bc1bc

Approved on: 2024-08-01

Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.122C>T

NM_001754.5(RUNX1):c.122C>T (p.Thr41Met)

NC_000021.9:g.34887072G>A

CM000683.2:g.34887072G>A

NC_000021.8:g.36259369G>A

CM000683.1:g.36259369G>A

NC_000021.7:g.35181239G>A

NG_011402.2:g.1102640C>T

ENST00000675419.1:c.122C>T

ENST00000300305.7:c.122C>T

ENST00000344691.8:c.41C>T

ENST00000358356.9:c.41C>T

ENST00000399237.6:c.86C>T

ENST00000399240.5:c.41C>T

ENST00000437180.5:c.122C>T

ENST00000455571.5:c.83C>T

ENST00000475045.6:c.122C>T

ENST00000482318.5:c.59-6359C>T

NM_001001890.2:c.41C>T

NM_001122607.1:c.41C>T

NM_001754.4:c.122C>T

NM_001001890.3:c.41C>T

NM_001122607.2:c.41C>T

Uncertain Significance

BA1 BS4 BS3 BS1 BS2 BP7 BP5 BP3 BP2 BP4 BP1 PVS1 PS1 PS2 PS4 PS3 PP4 PP1 PP3 PP2 PM6 PM2 PM5 PM1 PM4 PM3

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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.122C>T (p.Thr41Met) is a missense variant which does not meet any ACMG/AMP criteria. 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: None.

BA1

The variant is present in gnomAD v2.1.1 ONLY but does not meet code criteria (MAF 0.000009 (Eur Non-Finnish)

BS4

BS4 cannot be applied because there is no data available.

BS3

BS3 cannot be applied because there is no functional data available for this variant.

BS1

The variant is present in gnomAD v2.1.1 ONLY but does not meet code criteria (MAF 0.000009 (Eur Non-Finnish)

BS2

BS2 is not applicable since FPD/AML patients display incomplete penetrance and the average age of onset of hematologic malignancies is 33 years.

BP7

BP7 cannot be applied because this variant is a missense variant.

BP5

This rule is not applicable to the MMVCEP.

BP3

This rule is not applicable to the MMVCEP.

BP2

BP2 cannot be applied because there is no data available.

BP4

This missense variant has a REVEL score ≥ 0.50 (0.61) and SpliceAI score is ≤ 0.20 (0).

BP1

This rule is not applicable to the MMVCEP.

PVS1

PVS1 cannot be applied because this variant is a missense change.

PS1

PS1 cannot be applied because to our knowledge, there is no other missense variant determined to be pathogenic at this amino acid residue.

PS2

PS2 cannot be applied because there is no data available.

PS4

To our knowledge, this variant has not been reported in the literature in individuals affected with RUNX1-related conditions.

PS3

PS3 cannot be applied because there is no functional data available for this variant.

PP4

This rule is not applicable to the MMVCEP.

PP1

PP1 cannot be applied because there is no data available.

PP3

This missense variant has a REVEL score ≤ 0.88 (0.61) and SpliceAI score is ≤ 0.38 (0).

PP2

This rule is not applicable to the MMVCEP.

PM6

PM6 cannot be applied because there is no data available.

PM2

The highest population minor allele frequency in gnomAD v2.1.1 is 0.000009 in Eur Non-Finnish population.

PM5

PM5 cannot be applied because to our knowledge, there is no other missense variant determined to be pathogenic at this amino acid residue.

PM1

PM1 cannot be applied because this variant is not located in not located in AA residues 89-204.

PM4

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

PM3

This rule is not applicable to the MMVCEP.

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