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.249C>T (p.Ala83=)

CA512318889

1153047 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 55792a37-c1ea-4f3f-bfd7-8fba9ad57db5

HGVS expressions

NM_001754.5:c.249C>T

NM_001754.5(RUNX1):c.249C>T (p.Ala83=)

NC_000021.9:g.34886945G>A

CM000683.2:g.34886945G>A

NC_000021.8:g.36259242G>A

CM000683.1:g.36259242G>A

NC_000021.7:g.35181112G>A

NG_011402.2:g.1102767C>T

ENST00000675419.1:c.249C>T

ENST00000300305.7:c.249C>T

ENST00000344691.8:c.168C>T

ENST00000358356.9:c.168C>T

ENST00000399237.6:c.213C>T

ENST00000399240.5:c.168C>T

ENST00000437180.5:c.249C>T

ENST00000455571.5:c.210C>T

ENST00000482318.5:c.59-6232C>T

NM_001001890.2:c.168C>T

NM_001122607.1:c.168C>T

NM_001754.4:c.249C>T

NM_001001890.3:c.168C>T

NM_001122607.2:c.168C>T

Likely Benign

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

BP7 BP4 PM2_Supporting

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

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.249C>T (p.Ala83=) is a synonymous variant. REVEL score not calculable. SpliceAI predicts: Acceptor loss 0.00, Donor loss 0.00, Acceptor gain 0.00, Donor gain 0.00. (BP4) Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 0.324528 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). PM2_supporting: 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 0.324528 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

BP4

REVEL score not calculable. SpliceAI predicts: Acceptor loss 0.00, Donor loss 0.00, Acceptor gain 0.00, Donor gain 0.00. (BP4)

PM2_Supporting

PM2_supporting: This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2).

BP5

This rule is not applicable for MM-VCEP

BP2

No published literature could be found on this variant

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

PS2

No published literature could be found on this variant

PS4

No published literature could be found on this variant

PS3

No published literature could be found on this variant

PS1

Synonymous change, not applicable

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP1

No published literature could be found on this variant

PP4

This rule is not applicable for MM-VCEP

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP2

This rule is not applicable for MM-VCEP

PM1

This variant is outside the RHD.

PM5

Synonymous change, not applicable

PM3

This rule is not applicable for MM-VCEP

PM4

Synonymous variant, not applicable

PM6

No published literature could be found on this variant

PVS1

Synonymous change, not applicable

BS4

No published literature could be found on this variant

BS3

No published literature could be found on this variant

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS2

This rule is not applicable for MM-VCEP

Approved on: 2022-04-25

Published on: 2022-07-05

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