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]
Link to SEPIO compliant JSON-LD document
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001754.5(RUNX1):c.231C>T (p.Ser77=)

CA512318903

861921 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7ccaed33-76a7-4e66-86e3-4822111fde5f

HGVS expressions

NM_001754.5:c.231C>T
NM_001754.5(RUNX1):c.231C>T (p.Ser77=)
NC_000021.9:g.34886963G>A
CM000683.2:g.34886963G>A
NC_000021.8:g.36259260G>A
CM000683.1:g.36259260G>A
NC_000021.7:g.35181130G>A
NG_011402.2:g.1102749C>T
ENST00000675419.1:c.231C>T
ENST00000300305.7:c.231C>T
ENST00000344691.8:c.150C>T
ENST00000358356.9:c.150C>T
ENST00000399237.6:c.195C>T
ENST00000399240.5:c.150C>T
ENST00000437180.5:c.231C>T
ENST00000455571.5:c.192C>T
ENST00000482318.5:c.59-6250C>T
NM_001001890.2:c.150C>T
NM_001122607.1:c.150C>T
NM_001754.4:c.231C>T
NM_001001890.3:c.150C>T
NM_001122607.2:c.150C>T

Likely Benign

Met criteria codes 2
BS1 BP4
Not Met criteria codes 24
BA1 PVS1 BS4 BS3 BS2 BP7 BP5 BP2 BP3 BP1 PS2 PS4 PS3 PS1 PP1 PP4 PP3 PP2 PM1 PM5 PM3 PM4 PM6 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.231C>T (p.Ser77=) is a synonymous variant which has a MAF of 0.00001 (0.001%, 108718/243164, 1 allele) in the European (Non-Finnish) subpopulations of the gnomAD cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). No splicing impact or creation of cryptic splice sites is predicted by SSF and MES. SpliceAI predicts no impact to splicing (score: 0.00) (BP4). This variant was reported in ClinVar in 2022 by Invitae, but the affected status of the proband is unknown (Variation ID 861921). 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
MAF of 0.00001 (0.001%, 108718/243164, 1 allele) in the European (Non-Finnish) subpopulations of the gnomAD cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1).
BP4
No splicing impact or creation of cryptic splice sites predicted by SSF and MES. Splice AI predicts no impact to splicing (score: 0.00).
Not Met criteria codes
BA1
This rule is not applicable because BS1 is met.
PVS1
This rule is not applicable because the variant is not loss of function.
BS4
This rule is not applicable because there are no reports of this variant in other family members.
BS3
This rule is not applicable because there are no functional studies showing the damaging effect on protein function or splicing.
BS2
This rule is not applicable for MM-VCEP.
BP7
This rule is not applicable because UCSC gives this sysnonymous variant a phyloP score of 3.70931.
BP5
This rule is not applicable for MM-VCEP.
BP2
This rule is not applicable because variant is only seen once in gnomAD cohort.
BP3
This rule is not applicable for MM-VCEP.
BP1
This rule is not applicable for MM-VCEP.
PS2
This rule is not applicable because there are no reports of this variant in affected family members.
PS4
This rule is not applicable because there are no reports of this variant in any probands meeting at least one of the RUNX1-phenotypic criteria. This variant was reported in ClinVar in 2022 by Invitae but the affected status of the proband is unknown (Variation ID 861921).
PS3
This rule is not applicable because there are no functional studies supporting a damaging effect on the gene or gene product.
PS1
This rule is not applicable because the variant is not missense.
PP1
This rule is not applicable because there are no reports of this variant in other family members.
PP4
This rule is not applicable for MM-VCEP.
PP3
This rule is not applicable because the variant is not missense.
PP2
This rule is not applicable for MM-VCEP.
PM1
This variant does not affect one of the hotspot residues established by the MM-VCEP for RUNX1.
PM5
This rule is not applicable because the variant is not missense.
PM3
This rule is not applicable for MM-VCEP.
PM4
This rule is not applicable because the variant is not an inframe indel.
PM6
This rule is not applicable because there are no reports of this variant with assumed de novo occurrences.
PM2
This rule is not applicable because BS1 is met.
Approved on: 2024-06-24
Published on: 2024-06-24
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