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.336G>T (p.Leu112=)

CA320642610

698127 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 963a420f-4b4d-43e0-ae79-7fb4a577d632

HGVS expressions

NM_001754.5:c.336G>T

NM_001754.5(RUNX1):c.336G>T (p.Leu112=)

NC_000021.9:g.34886858C>A

CM000683.2:g.34886858C>A

NC_000021.8:g.36259155C>A

CM000683.1:g.36259155C>A

NC_000021.7:g.35181025C>A

NG_011402.2:g.1102854G>T

ENST00000675419.1:c.336G>T

ENST00000300305.7:c.336G>T

ENST00000344691.8:c.255G>T

ENST00000358356.9:c.255G>T

ENST00000399237.6:c.300G>T

ENST00000399240.5:c.255G>T

ENST00000437180.5:c.336G>T

ENST00000455571.5:c.297G>T

ENST00000482318.5:c.59-6145G>T

NM_001001890.2:c.255G>T

NM_001122607.1:c.255G>T

NM_001754.4:c.336G>T

NM_001001890.3:c.255G>T

NM_001122607.2:c.255G>T

Likely Benign

BP4 BP7

PVS1 BS2 BS4 BS3 BS1 BP2 BP1 BP3 BP5 PS4 PS3 PS1 PS2 BA1 PP4 PP3 PP2 PP1 PM3 PM1 PM4 PM5 PM2 PM6

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.336G>T (p.Leu112=) is a synonymous variant. This variant does not have a REVEL score and SpliceAI is ≤0.20 (0.01) which meets the criteria for BP4. Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.05 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). 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

BP4

This variant has a SpliceAI score ≤ 0.20 (0.01).

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.05 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

PVS1

This is a synonymous variant.

BS2

This rule is not applicable for MM-VCEP

BS4

Variant has not been reported in patients in literature.

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.

BS1

Highest MAF is not between 0.00015-0.0015 (European: 0.002%; .00002; 2/111564)

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

BP3

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

PS4

This variant has not been reported in patients in literature.

PS3

This variant has not been featured in in vitro or in vivo functional studies that show a damaging effect on protein function or splicing.

PS1

This variant is synonymous

PS2

This variant has not been reported in patients in literature.

BA1

Highest MAF is less than 0.0015 (0.15%) (European: 0.002%; .00002; 2/111564)

PP4

This rule is not applicable for MM-VCEP

PP3

This variant does not have a REVEL score of ≥ 0.88 nor does it impactfully alter a splice site.

PP2

This rule is not applicable for MM-VCEP

PP1

Variant has not been reported in patients in literature.

PM3

This rule is not applicable for the MM-VCEP.

PM1

This variant affects one of the other residues (AA 89-204) within the RHD, but it is synonymous, so it does not meet this code.

PM4

This variant does not change the length of the protein as it is a synonymous variant

PM5

This variant is synonymous

PM2

Variant is present in controls in gnomAD. Highest MAF is less than 0.0015 (0.15%) (European: 0.002%; 0.00002; 2/111564)

PM6

This variant has not been reported in patients in literature.

Approved on: 2022-08-23

Published on: 2023-11-13

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