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.300C>G (p.Ser100=)

CA512318845

463991 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e9ec7bd4-3aef-416c-9b22-48d87e0afa88

HGVS expressions

NM_001754.5:c.300C>G

NM_001754.5(RUNX1):c.300C>G (p.Ser100=)

NC_000021.9:g.34886894G>C

CM000683.2:g.34886894G>C

NC_000021.8:g.36259191G>C

CM000683.1:g.36259191G>C

NC_000021.7:g.35181061G>C

NG_011402.2:g.1102818C>G

ENST00000675419.1:c.300C>G

ENST00000300305.7:c.300C>G

ENST00000344691.8:c.219C>G

ENST00000358356.9:c.219C>G

ENST00000399237.6:c.264C>G

ENST00000399240.5:c.219C>G

ENST00000437180.5:c.300C>G

ENST00000455571.5:c.261C>G

ENST00000482318.5:c.59-6181C>G

NM_001001890.2:c.219C>G

NM_001122607.1:c.219C>G

NM_001754.4:c.300C>G

NM_001001890.3:c.219C>G

NM_001122607.2:c.219C>G

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

BP4 PM2_Supporting BP7

PS4 PS2 PS3 PS1 PM1 PM5 PM3 PM4 PM6 BA1 PVS1 BP2 BP3 BP1 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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.300C>G (p.Ser100=) is a synonymous variant. In summary, this variant meets the criteria to be classified as likely benign. Therefore, a REVEL score is not calculable. SpliceAI prediction suggests Acceptor loss 0, Donor loss 0, Acceptor gain 0, Donor gain 0. Therefore, there appears to be no effect on splicing (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.302402 < 2.0)(BP7 ). This variant is completely absent from all population databases with at least 20x coverage for RUNX1(PM2_supporting). ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, PM2_supporting.

BP4

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1. Therefore, PM2 is MET.

BP7

This is a synonymous variant with no effect on the final amino acid codon. Therefore, a REVEL score is not calculable. SpliceAI prediction suggests: Acceptor loss 0, Donor loss 0, Acceptor gain 0, Donor gain 0. Therefore, there appears to be no effect on splicing. Given the above, PP3 is NOT MET. Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.302402 < 2.0). Therefore, BP7 IS MET.

PS4

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no allele burden data from studies available. PS4 is NOT MET.

PS2

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no de novo data from studies available. PS2 is NOT MET.

PS3

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no functional studies available. BS3 is NOT MET.

PS1

This is not applicable for a synonymous variant

PM1

This is not applicable for a synonymous variant

PM5

This is not applicable for a synonymous variant

PM3

This rule is not applicable for MM-VCEP

PM4

This is a synonymous variant, which not result in a protein length altering variant. Therefore, PM4 is NOT MET.

PM6

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no de novo data from studies available. PM6 is NOT MET.

BA1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1. Therefore, BA1 is NOT MET.

PVS1

This is a synonymous variant, therefore PVS1 is NOT MET.

BP2

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no inheritance data from studies available. BP2 is NOT MET.

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

BS2

This rule is not applicable for MM-VCEP

BS4

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no segregation studies available. BS4 is NOT MET.

BS3

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no functional studies available. BS3 is NOT MET.

BS1

This variant is completely absent from all population databases with at least 20x coverage for RUNX1. Therefore, BS1 is NOT MET.

PP1

An extensive literature search of PubMed, Google Scholar, and Mastermind revealed no literature on this variant. Therefore, there are no segregation studies available. PP1 is NOT MET.

PP4

This rule is not applicable for MM-VCEP

PP3

PP2

This rule is not applicable for MM-VCEP

Approved on: 2022-07-07

Published on: 2022-07-07

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.