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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Variant: NM_001754.4(RUNX1):c.423G>A (p.Ser141=)

CA10014519

463996 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9ab1d255-0f11-4b19-833a-9c710a8ecc4e

HGVS expressions

NM_001754.4:c.423G>A
NM_001754.4(RUNX1):c.423G>A (p.Ser141=)
NC_000021.9:g.34880642C>T
CM000683.2:g.34880642C>T
NC_000021.8:g.36252939C>T
CM000683.1:g.36252939C>T
NC_000021.7:g.35174809C>T
NG_011402.2:g.1109070G>A
ENST00000675419.1:c.423G>A
ENST00000300305.7:c.423G>A
ENST00000344691.8:c.342G>A
ENST00000358356.9:c.342G>A
ENST00000399237.6:c.387G>A
ENST00000399240.5:c.342G>A
ENST00000437180.5:c.423G>A
ENST00000455571.5:c.384G>A
ENST00000482318.5:c.*13G>A
NM_001001890.2:c.342G>A
NM_001122607.1:c.342G>A
NM_001001890.3:c.342G>A
NM_001122607.2:c.342G>A
NM_001754.5:c.423G>A
NM_001754.5(RUNX1):c.423G>A (p.Ser141=)

Benign

The Expert Panel has overridden the computationally generated classification - "Likely Benign"
Met criteria codes 3
BS1 BP7 BP4
Not Met criteria codes 23
PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PVS1 BA1 BS4 BS3 BS2 PM3 PM1 PM5 PM4 PM6 PM2 BP5 BP2 BP3 BP1

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 NM_001754.4(RUNX1):c.423G>A (p.Ser141=) variant is 0.0001633 (0.016%, 5/30614 alleles, 251394 alleles) in the South Asian cohort (gnomAD), 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 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 addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score: -1.49 < 0.1 [-14.1;6.4]) (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: BS1, BP4, and BP7.
Met criteria codes
BS1
MAF of 0.0001633 (0.016%, 5/30614 alleles, 251394 alleles) in the South Asian cohort (gnomAD) is between 0.00015 (0.015%) and 0.0015 (0.15%). ALL:0.0024% (6/251394 alleles) - SAS:0.016% - NFE:0.00090%
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. In addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score: -1.49 < 0.1 [-14.1;6.4]).
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
PS2
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
PS3
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
PP4
Not applicable
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
PP2
Not applicable
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
MAF of 0.0001633 (0.016%, 5/30614 alleles, 251394 alleles) in the South Asian cohort (gnomAD) is between 0.00015 (0.015%) and 0.0015 (0.15%). ALL:0.0024% (6/251394 alleles) - SAS:0.016% - NFE:0.00090%
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
BS2
Not applicable
PM3
Not applicable
PM1
Not located at 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
PM4
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
PM2
MAF of 0.0001633 (0.016%, 5/30614 alleles, 251394 alleles) in the South Asian cohort (gnomAD) is between 0.00015 (0.015%) and 0.0015 (0.15%). ALL:0.0024% (6/251394 alleles) - SAS:0.016% - NFE:0.00090%
BP5
Not applicable
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
Not applicable
BP1
Not applicable
Approved on: 2022-07-05
Published on: 2022-07-05
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