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.98-1G>A

CA410204328

988809 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2d48476e-5ffa-4d05-b503-67d9a7552446

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.98-1G>A

NM_001754.5(RUNX1):c.98-1G>A

NC_000021.9:g.34887097C>T

CM000683.2:g.34887097C>T

NC_000021.8:g.36259394C>T

CM000683.1:g.36259394C>T

NC_000021.7:g.35181264C>T

NG_011402.2:g.1102615G>A

ENST00000675419.1:c.98-1G>A

ENST00000300305.7:c.98-1G>A

ENST00000344691.8:c.16G>A

ENST00000358356.9:c.16G>A

ENST00000399237.6:c.62-1G>A

ENST00000399240.5:c.16G>A

ENST00000437180.5:c.98-1G>A

ENST00000455571.5:c.59-1G>A

ENST00000475045.6:c.98-1G>A

ENST00000482318.5:c.59-6384G>A

NM_001001890.2:c.16G>A

NM_001122607.1:c.16G>A

NM_001754.4:c.98-1G>A

NM_001001890.3:c.16G>A

NM_001122607.2:c.16G>A

Uncertain Significance

PM2_Supporting PS4_Moderate

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

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.98-1G>A is a splice acceptor variant which only affects isoform c (PVS1_NA). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant has been reported in two probands meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 27479822, 29932212). In summary, this variant meets the criteria to be classified as a variant of unknown significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, PS4_Moderate.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

PS4_Moderate

This variant has been reported in two probands meeting at least one of the RUNX1-phenotypic criteria (PS4_Moderate; PMID: 27479822, 29932212)

BS2

This rule is not applicable for MM-VCEP

PVS1

This variant causes a single nucleotide change without a frameshift at the c.98 intron 3 acceptor site which only affects isoform c, PVS1_N/A as per the VCEP splicing table (PVS1_NA).

BS3

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

BS4

Segregation was not found to be absent in two or more informative meiosis.

BS1

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

BP7

This variant is a splicing variant at a canonical splice site.

BP5

This rule is not applicable for MM-VCEP.

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 variant occurs at a canonical splice site so BP4 cannot be applied.

BP1

This rule is not applicable for MM-VCEP

PS2

De novo data for this variant has not been reported in literature.

PS1

This variant is not a missense, synonymous, or frameshift variant.

PS3

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

PP4

This rule is not applicable for MM-VCEP.

PP3

This variant occurs at a canonical splice site so PP5 cannot be applied.

PP2

This rule is not applicable for MM-VCEP

PP1

This variant was found to co-segregate with the disease in multiple affected family members, with two (2) meioses observed in one family, therefore it does not meet PP1 as 3 meiosis are required. PMID:27479822 , PMID:32935436

BA1

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

PM6

De novo data for this variant has not been reported in literature.

PM5

This variant is not a missense, synonymous, or frameshift variant.

PM1

This variant is not a missense variant.

PM3

This rule is not applicable for MM-VCEP.

PM4

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

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