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.508+4C>A

CA10014500

2174248 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ae7e2066-38fa-45a0-8733-4e169b0f1df9

HGVS expressions

NM_001754.5:c.508+4C>A

NM_001754.5(RUNX1):c.508+4C>A

NC_000021.9:g.34880553G>T

CM000683.2:g.34880553G>T

NC_000021.8:g.36252850G>T

CM000683.1:g.36252850G>T

NC_000021.7:g.35174720G>T

NG_011402.2:g.1109159C>A

ENST00000675419.1:c.508+4C>A

ENST00000300305.7:c.508+4C>A

ENST00000344691.8:c.427+4C>A

ENST00000358356.9:c.427+4C>A

ENST00000399237.6:c.472+4C>A

ENST00000399240.5:c.427+4C>A

ENST00000437180.5:c.508+4C>A

ENST00000482318.5:c.*98+4C>A

NM_001001890.2:c.427+4C>A

NM_001122607.1:c.427+4C>A

NM_001754.4:c.508+4C>A

NM_001001890.3:c.427+4C>A

NM_001122607.2:c.427+4C>A

Likely Benign

BP7 BP4

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

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

The NM_001754.5(RUNX1):c.508+4C>A is a variant is located in Intron 5. It affects a nucleotide within the consensus splice site. However, splice prediction algorithms do not predict an effect on splicing (BP4). This variant is present at a MAF of 0.00006 (0.006%, 1/16256 alleles) in the African/African American population of gnomADv2.1.1. The nucleotide is not highly conserved with a phyloP score of -2.61. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal dominant hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: BP4, BP7.

BP7

No splicing effect and phyloP = -2.61

BP4

No predicted splicing effect

PS4

No case study found

PS2

No case study found

PS1

Intronic Variant

PS3

No studies found

PP1

No case study found

PP3

BP4 Met

PP2

This rule is not applicable for MM-VCEP

PP4

This rule is not applicable for MM-VCEP

PVS1

This is not a LOF variant

BA1

This variant is present at a MAF of 0.00006 ( 0.006%, 1/16256 alleles) in the African/African American population of gnomADv2.1.1

BS4

No case study found

BS3

No studies found

BS1

This variant is present at a MAF of 0.00006 ( 0.006%, 1/16256 alleles) in the African/African American population of gnomADv2.1.1

BS2

This rule is not applicable for MM-VCEP

PM5

Intronic Variant

PM4

Intronic variant

PM1

The variant is not present in a hot spot

PM3

This rule is not applicable for MM-VCEP

PM6

No case study found

PM2

This variant is present at a MAF of 0.00006 ( 0.006%, 1/16256 alleles) in the African/African American population of gnomADv2.1.1

BP5

This rule is not applicable for MM-VCEP

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP2

No case study found

Approved on: 2024-06-24

Published on: 2024-06-24

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