Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001754.5(RUNX1):c.744C>T (p.Asn248=)

CA512318594

532682 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4fbea03e-7dd2-4112-af41-3bea74ee084b
Approved on: 2024-10-29
Published on: 2024-10-29

HGVS expressions

NM_001754.5:c.744C>T
NM_001754.5(RUNX1):c.744C>T (p.Asn248=)
NC_000021.9:g.34834471G>A
CM000683.2:g.34834471G>A
NC_000021.8:g.36206768G>A
CM000683.1:g.36206768G>A
NC_000021.7:g.35128638G>A
NG_011402.2:g.1155241C>T
ENST00000675419.1:c.744C>T
ENST00000300305.7:c.744C>T
ENST00000344691.8:c.663C>T
ENST00000358356.9:c.663C>T
ENST00000399237.6:c.708C>T
ENST00000399240.5:c.532+25003C>T
ENST00000437180.5:c.744C>T
ENST00000469087.1:n.280C>T
ENST00000482318.5:c.*334C>T
NM_001001890.2:c.663C>T
NM_001122607.1:c.663C>T
NM_001754.4:c.744C>T
NM_001001890.3:c.663C>T
NM_001122607.2:c.663C>T
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Uncertain Significance

Met criteria codes 2
PM2_Supporting BP4
Not Met criteria codes 24
PS3 PS1 PS4 PS2 PP4 PP1 PP3 PP2 PVS1 PM5 PM3 PM1 PM4 PM6 BA1 BS2 BS3 BS4 BS1 BP5 BP7 BP2 BP3 BP1

Evidence Links 0

Expert Panel

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.744C>T (p.Asn248=) is a synonymous variant predicted by SSF and MES to lead to either an increase or a decrease in the canonical splice site score by no more than 10%, with no putative cryptic splice sites created (BP4). However, evolutionary conservation algorithms predict the site as being moderately conserved (PhyloP score: 2.55) and the variant is not the reference nucleotide in one primate and/or three mammal species. This variant is also absent from population databases (PM2_supporting). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PM2_supporting.
Met criteria codes
PM2_Supporting
Absent from gnomAD v2 and v3
BP4
This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created.
Not Met criteria codes
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Not applicable
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
Not applicable
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Not applicable
PM1
Not located at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 105-204.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
Not applicable
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
Not applicable
BP7
This synonymous is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created. However, evolutionary conservation prediction algorithms predict the site as being moderately conserved (PhyloP score: 2.55 < 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
Not applicable
BP1
Not applicable
Curation History
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