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]

Variant: NM_001754.5(RUNX1):c.613+14C>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA2573157345

1597566 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 42b26001-7bd7-4d32-8c95-f95452af2662

Approved on: 2024-06-24

Published on: 2024-06-24

HGVS expressions

NM_001754.5:c.613+14C>G

NM_001754.5(RUNX1):c.613+14C>G

NC_000021.9:g.34859460G>C

CM000683.2:g.34859460G>C

NC_000021.8:g.36231757G>C

CM000683.1:g.36231757G>C

NC_000021.7:g.35153627G>C

NG_011402.2:g.1130252C>G

ENST00000675419.1:c.613+14C>G

ENST00000300305.7:c.613+14C>G

ENST00000344691.8:c.532+14C>G

ENST00000358356.9:c.532+14C>G

ENST00000399237.6:c.577+14C>G

ENST00000399240.5:c.532+14C>G

ENST00000437180.5:c.613+14C>G

ENST00000467577.1:n.105+14C>G

ENST00000482318.5:c.*203+14C>G

NM_001001890.2:c.532+14C>G

NM_001122607.1:c.532+14C>G

NM_001754.4:c.613+14C>G

NM_001001890.3:c.532+14C>G

NM_001122607.2:c.532+14C>G

Likely Benign

PM2_Supporting BP7 BP4

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

Evidence Links 2

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.613+14C>G is an intronic variant. This variant is absent from gnomAD v2.1.1 (mean depth of coverage > 60) and from gnomAD v3.1.1 (mean depth of coverage 30) (PM2_Supporting). It is not predicted by SpliceAI to impact splicing (≤0.20). In addition, it occurs at a nucleotide that is not conserved as shown by phyloP100 (0.09) (BP4, 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, PM2_supporting.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (mean depth of coverage > 60 for exome and genome combined) and from gnomAD v3.1.1 (mean depth of coverage 30).

BP7

The c.613+14C>G (p.?) variant (NM_001754.5) is a synonymous variant that is not predicted by SpliceAI to impact splicing (≤0.20). In addition, it occurs at a nucleotide that is not conserved as shown by phyloP100 (0.09) (BP4, BP7).

BP4

This is an intronic variant therefore no REVEL score is applicable and SpliceAI score is ≤0.20 (0) (BP4).

PVS1

This variant is not a null variant.

PS1

This is an intronic variant.

PS2

To our knowledge, no publication has reported this variant as de novo to date.

PS4

To our knowledge, no publication has reported this variant to date. Clinvar has an entry for this variant but the affected status is unknown.

PS3

To our knowledge, this synonymous variant was not evaluated in transactivation assays.

not evaluated PubMed:33692461

not evaluated PubMed:34166225

BA1

This variant is absent from gnomAD v2.1.1 (mean depth of coverage > 60 for exome and genome combined) and from gnomAD v3.1.1 (mean depth of coverage 30).

PP4

This rule is not applicable to the MMVCEP

PP1

To our knowledge, no publication has reported this variant to date. Clinvar has an entry for this variant but the affected status is unknown.

PP3

This is an intronic variant therefore no REVEL score is applicable and SpliceAI score is <0.38 (0) (PP3).

PP2

This rule is not applicable to the MMVCEP.

PM6

To our knowledge, no publication has reported this variant as de novo to date.

PM5

This is an intronic variant.

PM3

This rule is not applicable to the MMVCEP

PM1

This is an intronic variant.

PM4

This is not an in-frame deletion/insertion.

BS4

To our knowledge, no publication has reported this variant to date. Clinvar has an entry for this variant but the affected status is unknown.

BS3

To our knowledge, this synonymous variant was not evaluated in transactivation assays.

not evaluated PubMed:33692461

not evaluated PubMed:34166225

BS1

This variant is absent from gnomAD v2.1.1 (mean depth of coverage > 60 for exome and genome combined) and from gnomAD v3.1.1 (mean depth of coverage 30).

BS2

This rule is not applicable to the MMVCEP.

BP5

This rule is not applicable to the MMVCEP

BP2

To our knowledge, no publication has reported this information to date.

BP3

This rule is not applicable to the MMVCEP

BP1

This rule is not applicable to the MMVCEP.

Curation History

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