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.508+1G>T

CA410202461

988808 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7c3203df-2036-41f0-8698-b467234e6d4b

HGVS expressions

NM_001754.5:c.508+1G>T

NM_001754.5(RUNX1):c.508+1G>T

NC_000021.9:g.34880556C>A

CM000683.2:g.34880556C>A

NC_000021.8:g.36252853C>A

CM000683.1:g.36252853C>A

NC_000021.7:g.35174723C>A

NG_011402.2:g.1109156G>T

ENST00000675419.1:c.508+1G>T

ENST00000300305.7:c.508+1G>T

ENST00000344691.8:c.427+1G>T

ENST00000358356.9:c.427+1G>T

ENST00000399237.6:c.472+1G>T

ENST00000399240.5:c.427+1G>T

ENST00000437180.5:c.508+1G>T

ENST00000482318.5:c.*98+1G>T

NM_001001890.2:c.427+1G>T

NM_001122607.1:c.427+1G>T

NM_001754.4:c.508+1G>T

NM_001001890.3:c.427+1G>T

NM_001122607.2:c.427+1G>T

Likely Pathogenic

PVS1 PM2_Supporting

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

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.508+1G>T is a splicing variant which is predicted to alter splicing. This variant affects intron 5 at the canonical Donor site c.508 (SpliceAI value = Donor Loss 1.00) (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

PVS1

This variant affects intron 5 at the canonical Donor site c.508 (SpliceAI value = Donor Loss 1.00)

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

PS4

This variant has not been reported in probands.

PS2

This variant has not been found to co-segregate with the disease in the literature.

PS1

This variant is not a missense variant.

PS3

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PM5

This variant is not a missense variant.

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 NOR is it within residues 89-204

PM3

This rule is not applicable for MM-VCEP

PM4

This variant is not an indel.

PM6

This variant has not been reported in probands in the literature

BA1

Variant is not present in population databases (gnomAD v2.1 or v3.1.2)

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

BP3

This rule is not applicable for MM-VCEP

BP4

This synonymous/intronic variant has a SpliceAI score ≥ 0.20 (Donor Loss 1.00).

BP1

This rule is not applicable for MM-VCEP

BP7

BP7: This variant impacts a splice site.

BP5

This rule is not applicable for MM-VCEP

BS2

This rule is not applicable for MM-VCEP

BS4

This variant has not been reported in affected family members.

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

BS1

Variant is not present in population databases (gnomAD v2.1 or v3.1.2)

PP1

This variant has not been reported in affected family members.

PP4

This rule is not applicable for MM-VCEP

PP3

This intronic variant has a SpliceAI score of ≥ 0.38 (Donor Loss 1.00). However, with PVS1 applied, PP3 cannot be applied.

PP2

This rule is not applicable for MM-VCEP

Approved on: 2023-12-09

Published on: 2023-12-09

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