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]

Variant: NM_001754.5(RUNX1):c.613+108G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014446

1219872 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e5e3150c-8593-41b4-b9c7-ef6ab87624f5

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.613+108G>A

NM_001754.5(RUNX1):c.613+108G>A

NC_000021.9:g.34859366C>T

CM000683.2:g.34859366C>T

NC_000021.8:g.36231663C>T

CM000683.1:g.36231663C>T

NC_000021.7:g.35153533C>T

NG_011402.2:g.1130346G>A

ENST00000675419.1:c.613+108G>A

ENST00000300305.7:c.613+108G>A

ENST00000344691.8:c.532+108G>A

ENST00000358356.9:c.532+108G>A

ENST00000399237.6:c.577+108G>A

ENST00000399240.5:c.532+108G>A

ENST00000437180.5:c.613+108G>A

ENST00000467577.1:n.105+108G>A

ENST00000482318.5:c.*203+108G>A

NM_001001890.2:c.532+108G>A

NM_001122607.1:c.532+108G>A

NM_001754.4:c.613+108G>A

NM_001001890.3:c.532+108G>A

NM_001122607.2:c.532+108G>A

Benign

BP7 BP4 BA1

PP1 PP4 PP3 PP2 PM6 PM2 PM1 PM5 PM3 PM4 BS2 BS4 BS3 BS1 BP5 BP2 BP3 BP1 PVS1 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.613+108G>A is a noncoding (intronic) variant. This variant has a MAF of 0.00244 (0.244%, 646/265052, 547 alleles) in the African subpopulation of the gnomAD v2.1.1 cohort, which is ≥ 0.0015 (0.15%) (BA1). No splicing impact or creation of cryptic splice sites is predicted by SSF and MES. SpliceAI predicts no impact to splicing (score: 0) (BP4). Evolutionary conservation algorithms predict the site as not being conserved (PhyloP score -0.18222 < 2.0) (BP7). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4, BP7.

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.18222 < 2.0).

BP4

No splicing impact or creation of cryptic splice sites predicted by SSF and MES. Splice AI predicts no impact to splicing (score: 0).

BA1

MAF of 0.00244 (0.244%, 646/265052, 547 alleles) in the African subpopulation of the gnomAD v2.1.1 cohort is ≥ 0.0015 (0.15%).

PP1

This variant has no data demonstrating cosegregation with disease in multiple affected family members in RUNX1.

PP4

This rule is not applicable for MM-VCEP.

PP3

This noncoding variant does not have a splicing impact or creation of cryptic splice sites as predicted by SSF and MES.

PP2

This rule is not applicable for MM-VCEP.

PM6

This variant does not have data on probands meeting at least one of the RUNX1-phenotypic criteria with assumed de novo occurrences.

PM2

This variant is present in gnomAD v2.1.1 cohort.

PM1

This noncoding variant does not affect one of the hotspot residues established by the MM-VCEP for RUNX1.

PM5

This noncoding variant is not at the same residue as other pathogenic variants based on MM-VCEP rules for RUNX1.

PM3

This rule is not applicable for MM-VCEP.

PM4

This noncoding variant does not affect one of the hotspot residues or at least one of the other residues (AA 89-204) within the RHD established by the MM-VCEP for RUNX1.

BS2

This rule is not applicable for MM-VCEP.

BS4

This variant has no data demonstrating segregation in affected family members.

BS3

This variant has no functional studies demonstrating damaging effect on protein function or splicing.

BS1

MAF of 0.00244 (0.244%, 646/265052, 547 alleles) in the African subpopulation of the gnomAD v2.1.1 cohort is not between 0.00015 (0.015%) and 0.0015 (0.15%).

BP5

This rule is not applicable for MM-VCEP.

BP2

This variant does not have any observed cases reported in the literature.

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

PVS1

This is a noncoding (intronic) variant with no splicing effects.

PS2

This variant does not have data on cases in patients with the disease and no family history.

PS4

This rule is not applicable because there is no published information on affected individuals nor a RUNX1 case control study. This variant was reported in ClinVar in 2019 by GeneDX but the affected status of the proband is unknown (Variation ID 1219872).

PS3

This variant has no functional studies demonstrating damaging effect on the gene or gene product.

PS1

This noncoding variant is not at the same amino acid change as other pathogenic variants based on MM-VCEP rules for RUNX1.

Curation History

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