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]
  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.927C>T (p.Gly309=)

CA10014267

239057 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3c85011e-8c15-400c-8b7a-b1f61ba36c3f
Approved on: 2021-01-12
Published on: 2021-01-12

HGVS expressions

NM_001754.4:c.927C>T
NM_001754.4(RUNX1):c.927C>T (p.Gly309=)
NM_001001890.2:c.846C>T
NM_001001890.3:c.846C>T
NM_001754.5:c.927C>T
ENST00000300305.7:c.927C>T
ENST00000344691.8:c.846C>T
ENST00000399240.5:c.654C>T
ENST00000437180.5:c.927C>T
ENST00000482318.5:c.*517C>T
NC_000021.9:g.34799341G>A
CM000683.2:g.34799341G>A
NC_000021.8:g.36171638G>A
CM000683.1:g.36171638G>A
NC_000021.7:g.35093508G>A
NG_011402.2:g.1190371C>T
More

Benign

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

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 the variant is predicted by SSF and MES to create a putative cryptic donor splice site at c.925 (insignificant prediction by SpliceAI), evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 1.25 > 0.1 [-14.1;6.4]), and the variant is not the reference nucleotide in one primate and/or three mammal species, SSF and MES predict either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10%. 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 and BP2.
Met criteria codes
BA1
ALL:0.38% (1061/282896 alleles) - AFR:3.89% (941 het and 15 hom) - AMR:0.21% (74) - NFE:0.0062% (8) - OTH:0.11% (8) (gnomAD v2) ALL:0.38% (1570/282896 alleles) - AFR:3.572% (1458 het and 22 hom) - AMR:0.2856% (39) - NFE:0.01394% (9) - OTH:0.9285% (20) (gnomAD v3)
BP2
Variant found in homozygosity in population database/internal lab: AFR:15 hom (gnomAD v2) and AFR:22 hom (gnomAD v3).
Not Met criteria codes
PVS1
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
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
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%. However, they predict the creation of a putative cryptic donor splice site at c.925.
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
ALL:0.38% (1061/282896 alleles) - AFR:3.89% (941 het and 15 hom) - AMR:0.21% (74) - NFE:0.0062% (8) - OTH:0.11% (8) (gnomAD v2) ALL:0.38% (1570/282896 alleles) - AFR:3.572% (1458 het and 22 hom) - AMR:0.2856% (39) - NFE:0.01394% (9) - OTH:0.9285% (20) (gnomAD v3)
PM6
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.
BS1
ALL:0.38% (1061/282896 alleles) - AFR:3.89% (941 het and 15 hom) - AMR:0.21% (74) - NFE:0.0062% (8) - OTH:0.11% (8) (gnomAD v2) ALL:0.38% (1570/282896 alleles) - AFR:3.572% (1458 het and 22 hom) - AMR:0.2856% (39) - NFE:0.01394% (9) - OTH:0.9285% (20) (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
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%. However, they predict the creation of a putative cryptic donor splice site at c.925, evolutionary conservation prediction algorithms predict the site as being weakly conserved (PhyloP score: 1.25 > 0.1 [-14.1;6.4]), and the variant is not 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%. However, they predict the creation of a putative cryptic donor splice site at c.925 (SpliceAI does not show a significant score for this prediction).
Curation History
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