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.705C>T (p.Ala235=)

CA320603683

532686 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0296c915-483d-450c-bd77-48afc65e46a6
Approved on: 2020-04-10
Published on: 2020-06-02

HGVS expressions

NM_001754.4:c.705C>T
NM_001754.4(RUNX1):c.705C>T (p.Ala235=)
NC_000021.9:g.34834510G>A
CM000683.2:g.34834510G>A
NC_000021.8:g.36206807G>A
CM000683.1:g.36206807G>A
NC_000021.7:g.35128677G>A
NG_011402.2:g.1155202C>T
NM_001001890.2:c.624C>T
NM_001122607.1:c.624C>T
NM_001001890.3:c.624C>T
NM_001122607.2:c.624C>T
ENST00000300305.7:c.705C>T
ENST00000344691.8:c.624C>T
ENST00000358356.9:c.624C>T
ENST00000399237.6:c.669C>T
ENST00000399240.5:c.532+24964C>T
ENST00000437180.5:c.705C>T
ENST00000469087.1:n.241C>T
ENST00000482318.5:c.*295C>T

Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 17
PVS1 BA1 BP7 BP2 BS1 BS3 BS4 PP3 PP1 PS3 PS4 PS1 PM4 PM1 PM5 PM2 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: 0.93 < 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species. 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.
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.
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
ALL:0.00071% (2/282376 alleles) - NFE:0.0016% (2) (gnomAD v2) ALL:0.0001397% (2/143146 alleles) - NFE:0.003099% (2) (gnomAD v3)
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: 0.93 < 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
BS1
ALL:0.00071% (2/282376 alleles) - NFE:0.0016% (2) (gnomAD v2) ALL:0.0001397% (2/143146 alleles) - NFE:0.003099% (2) (gnomAD v3)
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
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
PS3
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
PS1
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 in 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
PM2
ALL:0.00071% (2/282376 alleles) - NFE:0.0016% (2) (gnomAD v2) ALL:0.0001397% (2/143146 alleles) - NFE:0.003099% (2) (gnomAD v3)
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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