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NM_001754.5(RUNX1):c.99T>C (p.Asp33=) AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jul 25, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002056877.8

Allele description [Variation Report for NM_001754.5(RUNX1):c.99T>C (p.Asp33=)]

NM_001754.5(RUNX1):c.99T>C (p.Asp33=)

Gene:
RUNX1:RUNX family transcription factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.12
Genomic location:
Preferred name:
NM_001754.5(RUNX1):c.99T>C (p.Asp33=)
Other names:
NM_001754.5(RUNX1):c.99T>C; p.Asp33=
HGVS:
  • NC_000021.9:g.34887095A>G
  • NG_011402.2:g.1102617T>C
  • NM_001001890.3:c.18T>C
  • NM_001122607.2:c.18T>C
  • NM_001754.5:c.99T>CMANE SELECT
  • NP_001001890.1:p.Asp6=
  • NP_001116079.1:p.Asp6=
  • NP_001745.2:p.Asp33=
  • NP_001745.2:p.Asp33=
  • LRG_482t1:c.99T>C
  • LRG_482:g.1102617T>C
  • LRG_482p1:p.Asp33=
  • NC_000021.8:g.36259392A>G
  • NM_001754.4:c.99T>C
Links:
dbSNP: rs762090330
NCBI 1000 Genomes Browser:
rs762090330
Molecular consequence:
  • NM_001001890.3:c.18T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001122607.2:c.18T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001754.5:c.99T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Synonyms:
Platelet disorder, Aspirin-like; Familial platelet disorder with associated myeloid malignancy; Familial Platelet Disorder with Propensity to Acute Myelogenous Leukemia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0100083; MeSH: C563324; MedGen: C1832388; Orphanet: 71290; OMIM: 601399

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002490663Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely benign
(Aug 9, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005196551ClinGen Myeloid Malignancy Variant Curation Expert Panel
reviewed by expert panel

(ClinGen MyeloMalig ACMG Specifications v2)
Uncertain Significance
(Jul 25, 2024)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002490663.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen Myeloid Malignancy Variant Curation Expert Panel, SCV005196551.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_001754.5(RUNX1):c.99T>C (p.Asp33=) is a synonymous variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant has a SpliceAI predicted acceptor loss of 0.32, which indicates it may impact splicing (BP4/BP7 not applied). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024