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+158C>T

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014432

1199613 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f43554f2-011a-458c-a2e6-5170bfdf9648

Approved on: 2024-08-28

Published on: 2024-08-28

HGVS expressions

NM_001754.5:c.613+158C>T

NM_001754.5(RUNX1):c.613+158C>T

NC_000021.9:g.34859316G>A

CM000683.2:g.34859316G>A

NC_000021.8:g.36231613G>A

CM000683.1:g.36231613G>A

NC_000021.7:g.35153483G>A

NG_011402.2:g.1130396C>T

ENST00000675419.1:c.613+158C>T

ENST00000300305.7:c.613+158C>T

ENST00000344691.8:c.532+158C>T

ENST00000358356.9:c.532+158C>T

ENST00000399237.6:c.577+158C>T

ENST00000399240.5:c.532+158C>T

ENST00000437180.5:c.613+158C>T

ENST00000467577.1:n.105+158C>T

ENST00000482318.5:c.*203+158C>T

NM_001001890.2:c.532+158C>T

NM_001122607.1:c.532+158C>T

NM_001754.4:c.613+158C>T

NM_001001890.3:c.532+158C>T

NM_001122607.2:c.532+158C>T

Benign

BA1 BP2 BP4 BP7

PP1 PP4 PP3 PP2 PM1 PM5 PM3 PM4 PM6 PM2 PVS1 BS2 BS4 BS3 BS1 BP3 BP1 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.613+158C>T is an intronic variant which has a MAF of 0.03363 (3.4%, 595/17690 alleles) in the African subpopulation of the gnomAD v2 cohort, meeting the threshold of ≥ 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in an individual or in a population database (gnomAD v2) (BP2). It has a SpliceAI score ≤ 0.20 (0.0) (BP4), and evolutionary conservation algorithms predict the site as not being conserved, with a PhyloP score ≤ 2.0 (-0.58) (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, BP2, BP4, BP7.

BA1

MAF of 0.03363 (3.4%, 595/17690 alleles) in the African subpopulation of the gnomAD v2 cohort is ≥ 0.0015 (0.15%) (BA1).

BP2

This variant is detected in a homozygous state in an individual or in a population database (gnomAD v2).

BP4

This intronic variant has a SpliceAI score ≤ 0.20 (0.0) (BP4).

BP7

This variant has a SpliceAI score ≤ 0.20 (0.0) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-0.58) (BP7).

PP1

Segregation data for this variant has not been reported in literature.

PP4

This rule is not applicable for MM-VCEP.

PP3

This variant occurs at a canonical splice site so pp3 cannot be applied.

PP2

This rule is not applicable for MM-VCEP.

PM1

This variant is not a missense variant.

PM5

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

PM3

This rule is not applicable for MM-VCEP.

PM4

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

PM6

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

PM2

This variant is present in at least one population database.

PVS1

This variant is not a null variant.

BS2

This rule is not applicable for MM-VCEP.

BS4

Segregation data for this variant has not been reported in literature.

BS3

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

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset, as this variant meets the BA1 threshold.

BP3

This rule is not applicable for MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

BP5

This rule is not applicable for MM-VCEP.

PS2

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

PS4

Proband data for this variant has not been reported in literature.

PS3

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

PS1

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

Curation History

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