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.183G>A (p.Pro61=)

CA208646

212088 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9c14a91f-704c-4baf-95d3-a804a2b9ec8e

HGVS expressions

NM_001754.4:c.183G>A
NM_001754.4(RUNX1):c.183G>A (p.Pro61=)
NC_000021.9:g.34887011C>T
CM000683.2:g.34887011C>T
NC_000021.8:g.36259308C>T
CM000683.1:g.36259308C>T
NC_000021.7:g.35181178C>T
NG_011402.2:g.1102701G>A
NM_001001890.2:c.102G>A
NM_001122607.1:c.102G>A
NM_001001890.3:c.102G>A
NM_001122607.2:c.102G>A
NM_001754.5:c.183G>A
ENST00000300305.7:c.183G>A
ENST00000344691.8:c.102G>A
ENST00000358356.9:c.102G>A
ENST00000399237.6:c.147G>A
ENST00000399240.5:c.102G>A
ENST00000437180.5:c.183G>A
ENST00000455571.5:c.144G>A
ENST00000482318.5:c.59-6298G>A

Benign

Met criteria codes 3
BA1 BP4 BP2
Not Met criteria codes 15
PS1 PS3 PS4 PM5 PM4 PM1 PM2 PM6 PVS1 BP7 BS1 BS3 BS4 PP3 PP1

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 present in gnomAD (v2 and v3) at an allele frequency >0.15% with at least >5 alleles in any general continental population (BA1); in addition, the variant was found in homozygosity in the population database (BP2). Although evolutionary conservation prediction algorithms predict the site as being moderately conserved (PhyloP score: 3.03 > 0.1 [-14.1;6.4]) and the variant is not the reference nucleotide in one primate and/or three mammal species, it 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). In summary, the clinical significance of this variant is benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2, and BP4.
Met criteria codes
BA1
ALL:0.14% (379/262036 alleles) - AFR:1.55% (343 het and 5 hom) - AMR:0.063% (22) - NFE:0.0025% (3) - OTH:0.015% (1) (gnomAD v2) ALL:0.4444% (637/143326 alleles) - AFR:1.458% (591 het and 11 hom) - AMR:0.08049% (11) - NFE:0.007742% (5) - OTH:0.3714% (8) (gnomAD 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.
BP2
Variant found in homozygosity in population database/internal lab: AFR:5 hom (gnomAD v2) and AFR:11 hom (gnomAD v3).
Not Met criteria codes
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
PS4
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 located at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 105-204.
PM2
ALL:0.14% (379/262036 alleles) - AFR:1.55% (343 het and 5 hom) - AMR:0.063% (22) - NFE:0.0025% (3) - OTH:0.015% (1) (gnomAD v2) ALL:0.4444% (637/143326 alleles) - AFR:1.458% (591 het and 11 hom) - AMR:0.08049% (11) - NFE:0.007742% (5) - OTH:0.3714% (8) (gnomAD v3)
PM6
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
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 moderately conserved (PhyloP score: 3.03 > 0.1 [-14.1;6.4]), and the variant is not the reference nucleotide in one primate and/or three mammal species.
BS1
ALL:0.14% (379/262036 alleles) - AFR:1.55% (343 het and 5 hom) - AMR:0.063% (22) - NFE:0.0025% (3) - OTH:0.015% (1) (gnomAD v2) ALL:0.4444% (637/143326 alleles) - AFR:1.458% (591 het and 11 hom) - AMR:0.08049% (11) - NFE:0.007742% (5) - OTH:0.3714% (8) (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
Approved on: 2020-08-08
Published on: 2021-01-12
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