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.180C>T (p.Ala60=)

CA10014575

463987 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: ead1df36-ba12-4c8b-806d-19994923f1ed

HGVS expressions

NM_001754.4:c.180C>T
NM_001754.4(RUNX1):c.180C>T (p.Ala60=)
NM_001001890.2:c.99C>T
NM_001122607.1:c.99C>T
NM_001001890.3:c.99C>T
NM_001122607.2:c.99C>T
NM_001754.5:c.180C>T
ENST00000300305.7:c.180C>T
ENST00000344691.8:c.99C>T
ENST00000358356.9:c.99C>T
ENST00000399237.6:c.144C>T
ENST00000399240.5:c.99C>T
ENST00000437180.5:c.180C>T
ENST00000455571.5:c.141C>T
ENST00000482318.5:c.59-6301C>T
NC_000021.9:g.34887014G>A
CM000683.2:g.34887014G>A
NC_000021.8:g.36259311G>A
CM000683.1:g.36259311G>A
NC_000021.7:g.35181181G>A
NG_011402.2:g.1102698C>T

Likely Benign

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

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, and although evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 1.66 > 0.1 [-14.1;6.4]), the variant is the reference nucleotide in one primate and/or three mammal species (BP4+BP7). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and BP7.
Met criteria codes
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. Although evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 1.66 > 0.1 [-14.1;6.4]), the variant is the reference nucleotide in one primate and/or three mammal species.
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
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
BP2
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
BA1
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
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Absent from gnomAD v2 and v3 with >20x coverage (even though it was present in 1/55962 Europeans in ExAC). However, present in heterozygosity in 1/4235 European Americans (0/2181 African Americans) in ESP.
PM6
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
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
Approved on: 2021-01-12
Published on: 2021-01-12
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