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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(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: 2020-04-10
Published on: 2020-06-02

HGVS expressions

NM_001754.4:c.744C>T
NM_001754.4(RUNX1):c.744C>T (p.Asn248=)
NM_001001890.2:c.663C>T
NM_001122607.1:c.663C>T
NM_001001890.3:c.663C>T
NM_001122607.2:c.663C>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
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

Uncertain Significance

Met criteria codes 2
BP4 PM2
Not Met criteria codes 16
BS1 BS4 BS3 BP2 BP7 PS4 PS1 PS3 BA1 PP3 PP1 PM6 PM4 PM1 PM5 PVS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
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 (BP4). 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. It is also absent from population databases (PM2). 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 and PM2.
Met criteria codes
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.
PM2
Absent from gnomAD v2 and v3
Not Met criteria codes
BS1
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
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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.
PS4
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
PS3
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
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
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
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not located at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 105-204.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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