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.210G>A (p.Lys70=)

CA512318917

1665576 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 32c5aaa8-5c4e-4795-994a-1cf11b655e40

HGVS expressions

NM_001754.5:c.210G>A
NM_001754.5(RUNX1):c.210G>A (p.Lys70=)
NC_000021.9:g.34886984C>T
CM000683.2:g.34886984C>T
NC_000021.8:g.36259281C>T
CM000683.1:g.36259281C>T
NC_000021.7:g.35181151C>T
NG_011402.2:g.1102728G>A
ENST00000675419.1:c.210G>A
ENST00000300305.7:c.210G>A
ENST00000344691.8:c.129G>A
ENST00000358356.9:c.129G>A
ENST00000399237.6:c.174G>A
ENST00000399240.5:c.129G>A
ENST00000437180.5:c.210G>A
ENST00000455571.5:c.171G>A
ENST00000482318.5:c.59-6271G>A
NM_001001890.2:c.129G>A
NM_001122607.1:c.129G>A
NM_001754.4:c.210G>A
NM_001001890.3:c.129G>A
NM_001122607.2:c.129G>A

Likely Benign

Met criteria codes 3
PM2_Supporting BP7 BP4
Not Met criteria codes 23
BA1 PVS1 BS4 BS3 BS1 BS2 BP5 BP2 BP1 BP3 PS1 PS2 PS4 PS3 PP1 PP4 PP3 PP2 PM5 PM1 PM3 PM4 PM6

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.210G>A (p.Lys70=) is a synonymous variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). No splicing impact or creation of cryptic splice sites is predicted by SSF and MES, and SpliceAI predicts no impact to splicing (score: 0.00) (BP4). Evolutionary conservation prediction algorithms show the variant as the reference nucleotide in one primate and/or three mammal species (BP7). This variant was reported in ClinVar in 2021 by Invitae, but the affected status of the proband is unknown (Variation ID 1665576). 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: BP4, BP7, PM2_supporting.
Met criteria codes
PM2_Supporting
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).
BP7
Evolutionary conservation prediction algorithms show the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).
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 variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).
PVS1
Not applicable because this is a synonymous variant.
BS4
This rule is not applicable because there is no segregation data information in affected members of a family.
BS3
This rule is not applicable because there are no functional studies for this variant.
BS1
This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).
BS2
This rule is not applicable for MM-VCEP.
BP5
This rule is not applicable for MM-VCEP.
BP2
This rule is not applicable because the variant is completely absent from all population databases.
BP1
This rule is not applicable for MM-VCEP.
BP3
This rule is not applicable for MM-VCEP.
PS1
Not applicable because this is a synonymous variant.
PS2
This rule is not applicable because there is no information on affected individuals nor the family.
PS4
This rule is not applicable because there is no published information on affected individuals nor a RUNX1 case control study. This variant was reported in Clinvar in 2021 by Invitae but the affected status of the proband is unknown (Variation ID 1665576).
PS3
This rule is not applicable because there are no functional studies for this variant.
PP1
This rule is not applicable because there is no segregation data information in affected members of a family.
PP4
This rule is not applicable for MM-VCEP.
PP3
This rule is not applicable because this synonymous variant must be evaluated using MES & SSF.
PP2
This rule is not applicable for MM-VCEP.
PM5
Not applicable because this is a synonymous variant.
PM1
This rule is not applicable because this is not a missense variant.
PM3
This rule is not applicable for MM-VCEP.
PM4
Not applicable because this is a synonymous variant.
PM6
This rule is not applicable because there is no information on affected individuals nor the family.
Approved on: 2024-06-24
Published on: 2024-06-24
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.