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.114C>T (p.Arg38=)

CA512318994

1114762 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 37856af3-6a77-4bd8-b814-ed2a47f9f926

Approved on: 2022-08-23

Published on: 2023-11-13

HGVS expressions

NM_001754.5:c.114C>T

NM_001754.5(RUNX1):c.114C>T (p.Arg38=)

NC_000021.9:g.34887080G>A

CM000683.2:g.34887080G>A

NC_000021.8:g.36259377G>A

CM000683.1:g.36259377G>A

NC_000021.7:g.35181247G>A

NG_011402.2:g.1102632C>T

ENST00000675419.1:c.114C>T

ENST00000300305.7:c.114C>T

ENST00000344691.8:c.33C>T

ENST00000358356.9:c.33C>T

ENST00000399237.6:c.78C>T

ENST00000399240.5:c.33C>T

ENST00000437180.5:c.114C>T

ENST00000455571.5:c.75C>T

ENST00000475045.6:c.114C>T

ENST00000482318.5:c.59-6367C>T

NM_001001890.2:c.33C>T

NM_001122607.1:c.33C>T

NM_001754.4:c.114C>T

NM_001001890.3:c.33C>T

NM_001122607.2:c.33C>T

Likely Benign

BP4 BP7 PM2_Supporting

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

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.114C>T (p.Arg38=) is a synonymous variant. Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.53< 2.0 or the variant is the reference nucleotide in one primate and three mammal species) (BP7). This synonymous variant has a SpliceAI score ≤ 0.20 (0.02). The variant is absent from gnomAD with mean of 20X coverage (gnomAD v2.1 or v3.1.2) (PM2_supporting). In summary, this variant meets the criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP7, BP4

BP4

This synonymous/intronic/UTR/frameshift variant has a SpliceAI score ≤ 0.20 (0.02).

BP7

: Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.53< 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species)

PM2_Supporting

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

BS2

This rule is not applicable for MM-VCEP

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

BS4

This variant has not been reported in affected family members.

BS1

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

BP3

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.

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

PVS1

This is a synonymous variant, not a null 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.

PS4

This variant has not been reported in probands.

PS2

This variant has not been reported in probands in the literature.

PS1

This is a synonymous variant.

PP1

This variant was not found to co-segregate with disease in multiple affected family members.

PP4

This rule is not applicable for MM-VCEP

PP3

This synonymous/intronic variant does not have a SpliceAI score of ≥ 0.38 (0.02).

PP2

This rule is not applicable for MM-VCEP

PM6

This variant has not been reported in probands in the literature.

PM5

There has not yet been a different missense change determined to be pathogenic at this amino acid residue, as this is variant is located in a non-coding region.

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

PM4

This in-frame deletion/insertion DOES NOT affect at least one of the other residues (AA 89-204) within the RHD, as it is at location AA 38

PM3

This rule is not applicable for MM-VCEP

BA1

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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.