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.770C>T (p.Thr257Ile)

CA410206725

464007 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e7e8c187-61df-4b77-b5bd-f517bafb6202

Approved on: 2024-08-01

Published on: 2024-08-01

HGVS expressions

NM_001754.5:c.770C>T

NM_001754.5(RUNX1):c.770C>T (p.Thr257Ile)

NC_000021.9:g.34834445G>A

CM000683.2:g.34834445G>A

NC_000021.8:g.36206742G>A

CM000683.1:g.36206742G>A

NC_000021.7:g.35128612G>A

NG_011402.2:g.1155267C>T

ENST00000675419.1:c.770C>T

ENST00000300305.7:c.770C>T

ENST00000344691.8:c.689C>T

ENST00000358356.9:c.689C>T

ENST00000399237.6:c.734C>T

ENST00000399240.5:c.532+25029C>T

ENST00000437180.5:c.770C>T

ENST00000469087.1:n.306C>T

ENST00000482318.5:c.*360C>T

NM_001001890.2:c.689C>T

NM_001122607.1:c.689C>T

NM_001754.4:c.770C>T

NM_001001890.3:c.689C>T

NM_001122607.2:c.689C>T

Uncertain Significance

PM2_Supporting

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

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:c.770C>T (p.Thr257Ile) is a missense variant located in exon 7 of RUNX1. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). 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: PM2_supporting.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting).

BA1

Absent from gnomAD (v2 and v3)

BS2

This rule is not applicable to the MMVCEP.

PVS1

This rule cannot be applied as this change is a missense variant.

BS4

These rule cannot be applied because there is no data available.

BS3

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

BS1

Absent from gnomAD (v2 and v3)

BP7

This variant is not synonymous.

BP5

This rule is not applicable to the MMVCEP.

BP3

This rule is not applicable to the MMVCEP.

BP2

These rule cannot be applied because there is no data available.

BP4

Splice AI 0.01 < 0.2 but REVEL score 0.596 > 0.5

BP1

This rule is not applicable to the MMVCEP.

PS2

These rule cannot be applied because there is no data available.

PS4

No case reported.

PS3

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

PS1

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

PP4

This rule is not applicable to the MMVCEP.

PP1

These rule cannot be applied because there is no data available.

PP3

REVEL score 0.596 < 0.88 Splice AI 0.01 < 0.38

PP2

This rule is not applicable to the MMVCEP.

PM6

These rule cannot be applied because there is no data available.

PM4

This rule is not applicable because this change is a missense variant.

PM3

This rule is not applicable because RUNX1 is associated with a dominant inheritance mode.

PM1

Not in AA 89-204

PM5

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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.