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.165G>A (p.Ala55=)

CA512318955

532681 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 01e24f51-2715-4a65-be17-9adaa7b8d808

HGVS expressions

NM_001754.4:c.165G>A
NM_001754.4(RUNX1):c.165G>A (p.Ala55=)
NM_001001890.2:c.84G>A
NM_001122607.1:c.84G>A
NM_001001890.3:c.84G>A
NM_001122607.2:c.84G>A
ENST00000300305.7:c.165G>A
ENST00000344691.8:c.84G>A
ENST00000358356.9:c.84G>A
ENST00000399237.6:c.129G>A
ENST00000399240.5:c.84G>A
ENST00000437180.5:c.165G>A
ENST00000455571.5:c.126G>A
ENST00000482318.5:c.59-6316G>A
NC_000021.9:g.34887029C>T
CM000683.2:g.34887029C>T
NC_000021.8:g.36259326C>T
CM000683.1:g.36259326C>T
NC_000021.7:g.35181196C>T
NG_011402.2:g.1102683G>A

Uncertain Significance

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

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 weakly conserved (PhyloP score: 0.77 < 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species. In addition, this variant is completely absent from all population databases with at least 20x coverage for RUNX1 (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, but g.36259326C>A (p.Ala55=) is present in gnomAD v2 [ALL: 0.0004316% (1/231692 alleles) - AMR: 0.002934% (1)]
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Not applicable
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
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
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. However, evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 0.77 < 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Not applicable
PS4
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
PM5
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 at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 105-204.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2020-04-10
Published on: 2020-06-02
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