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.654C>T (p.Ser218=)

CA10014384

239052 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4b6d6bcb-da2e-42b4-886e-38565501ee4a
Approved on: 2019-08-02
Published on: 2019-08-02

HGVS expressions

NM_001754.4:c.654C>T
NM_001754.4(RUNX1):c.654C>T (p.Ser218=)
NC_000021.9:g.34834561G>A
CM000683.2:g.34834561G>A
NC_000021.8:g.36206858G>A
CM000683.1:g.36206858G>A
NC_000021.7:g.35128728G>A
NG_011402.2:g.1155151C>T
NM_001001890.2:c.573C>T
NM_001122607.1:c.573C>T
ENST00000300305.7:c.654C>T
ENST00000344691.8:c.573C>T
ENST00000358356.9:c.573C>T
ENST00000399237.6:c.618C>T
ENST00000399240.5:c.532+24913C>T
ENST00000437180.5:c.654C>T
ENST00000469087.1:n.190C>T
ENST00000482318.5:c.*244C>T
More

Likely Benign

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

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The MAF of the synonymous variant, NM_001754.4:c.654C>T (p.Ser218=), is 0.00105 (0.1%, 36/34418 alleles) in the Latino subpopulation of the gnomAD cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This synonymous variant is predicted by SSF and MES to lead to 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, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BP4.
Met criteria codes
BS1
gnomAD Allele Frequency of Latino Subpopulation: 0.00105 (36 out of 34418 Alleles) > 0.00015
BP4
Synonymous variant for which 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% AND no putative cryptic splice sites are created.
Not Met criteria codes
BA1
gnomAD Allele Frequency of Latino Subpopulation: 0.00105 (36 out of 34418 Alleles) < 0.0015
BS4
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
BP2
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
phyloP100way: 4.58487 >0.1
PS4
PMID: 27106701, mutational analysis from peripheral blood cells, not confirmed germline variants. PS4 can not apply in combined with BS1.
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
PP1
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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