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>T (p.Ser100=)

CA10014554

707516 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c7d5f740-5db2-435d-ac7f-595b64ba0f04

HGVS expressions

NM_001754.5:c.300C>T

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

NC_000021.9:g.34886894G>A

CM000683.2:g.34886894G>A

NC_000021.8:g.36259191G>A

CM000683.1:g.36259191G>A

NC_000021.7:g.35181061G>A

NG_011402.2:g.1102818C>T

ENST00000675419.1:c.300C>T

ENST00000300305.7:c.300C>T

ENST00000344691.8:c.219C>T

ENST00000358356.9:c.219C>T

ENST00000399237.6:c.264C>T

ENST00000399240.5:c.219C>T

ENST00000437180.5:c.300C>T

ENST00000455571.5:c.261C>T

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

NM_001001890.2:c.219C>T

NM_001122607.1:c.219C>T

NM_001754.4:c.300C>T

NM_001001890.3:c.219C>T

NM_001122607.2:c.219C>T

Likely Benign

BP7 BP4 PM2_Supporting

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

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.300C>T (p.Ser100=) is a synonymous variant that is not predicted to impact splicing. Since it is a synonymous variant, there is no REVEL score, and SpliceAI is ≤ 0.20 (0.01 33bp Donor Gain) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.302402 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, PM2_supporting.

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score -0.302402 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

BP4

Synonymous variant therefore no REVEL score and SpliceAI is ≤0.20 (0.01 33bp Donor Gain)

PM2_Supporting

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

PS4

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

PS2

De novo 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

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

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

BP1

This rule is not applicable for MM-VCEP

PP1

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

PP4

This rule is not applicable for MM-VCEP

PP3

Synonymous variant therefore no REVEL score and SpliceAI is ≥0.38 (0.01 33bp Donor Gain)

PP2

This rule is not applicable for MM-VCEP

BA1

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

PM5

There has not yet been a different missense change determined to be pathogenic at this amino acid residue.

PM1

Not a missense variant

PM3

This rule is not applicable for MM-VCEP

PM4

Not an in-frame deletion/insertion

PM6

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

PVS1

Not a null or frameshift 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.

Approved on: 2024-06-24

Published on: 2024-06-24

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