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.98-20_98-18del

CA658799414

517187 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a25c99de-f2c1-46a5-a581-84790919971a

Approved on: 2024-08-12

Published on: 2024-08-12

HGVS expressions

NM_001754.5:c.98-20_98-18del

NM_001754.5(RUNX1):c.98-20_98-18del

NC_000021.9:g.34887118_34887120del

CM000683.2:g.34887118_34887120del

NC_000021.8:g.36259415_36259417del

CM000683.1:g.36259415_36259417del

NC_000021.7:g.35181285_35181287del

NG_011402.2:g.1102596_1102598del

ENST00000675419.1:c.98-20_98-18del

ENST00000300305.7:c.98-20_98-18del

ENST00000344691.8:c.-4_-2del

ENST00000358356.9:c.-4_-2del

ENST00000399237.6:c.62-20_62-18del

ENST00000399240.5:c.-4_-2del

ENST00000437180.5:c.98-20_98-18del

ENST00000455571.5:c.59-20_59-18del

ENST00000475045.6:c.98-20_98-18del

ENST00000482318.5:c.59-6403_59-6401del

NM_001001890.2:c.-4_-2del

NM_001122607.1:c.-4_-2del

NM_001754.4:c.98-20_98-18del

NM_001001890.3:c.-4_-2del

NM_001122607.2:c.-4_-2del

Uncertain Significance

BP4 PM2_Supporting

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

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.98-20_98-18del is an intronic variant which has a SpliceAI Δ score ≤ 0.20 (0.00 except for 0.05 at acceptor gain) (BP4). It is completely absent from all population databases (gnomAD v2.1.1, gnomAD v3.1.2, and ExAC v1.0) with at least 20x coverage for RUNX1 (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: BP4, PM2_Supporting.

BP4

This intronic variant has a SpliceAI Δ score ≤0.20 (0.00 except for 0.05 at acceptor gain) (BP4).

PM2_Supporting

This variant is completely absent from all population databases (gnomAD v2.1.1, gnomAD v3.1.2 and ExAC v1.0) with at least 20X coverage for RUNX1 (PM2_Supporting).

PP1

No reported cases of this variant identified.

PP4

This rule is not applicable for MM-VCEP.

PP3

This intronic variant has a SpliceAI Δ score ≤0.20 (0.00 except for 0.05 at acceptor gain).

PP2

This rule is not applicable for MM-VCEP.

PM1

This variant is not within the RHD as specified by MM-VCEP.

PM5

This is an intronic variant not predicted to result in an amino acid change.

PM3

This rule is not applicable for MM-VCEP.

PM4

This variant is not predicted to impact protein length.

BA1

This variant is completely absent from all population databases (gnomAD v2.1.1, gnomAD v3.1.2 and ExAC v1.0) with at least 20X coverage for RUNX1.

PM6

No reported cases of this variant identified.

BS2

This rule is not applicable for MM-VCEP.

BS4

No reported cases of this variant identified.

BS3

No functional studies of this variant identified.

BS1

This variant is completely absent from all population databases (gnomAD v2.1.1, gnomAD v3.1.2 and ExAC v1.0) with at least 20X coverage for RUNX1.

BP2

No reported cases of this variant identified.

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

PVS1

This intronic variant is not predicted to cause any loss of function.

BP7

This intronic variant has a SpliceAI Δ score ≤0.20 (0.00 except for 0.05 at acceptor gain) BUT It has a PhloP score of >2.0 (PhloP score ranged from 6.81254 to 8.05383 across the 3 nucleotides as per USCS) and these 3 nucleotides were conserved across primates and mammals.

BP5

This rule is not applicable for MM-VCEP.

PS2

No reported cases of this variant identified.

PS4

No reported cases of this variant identified.

PS3

No functional studies of this variant identified.

PS1

This is an intronic variant not predicted to result in an amino acid change.

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