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NM_001754.5(RUNX1):c.145C>G (p.Pro49Ala) AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 13, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003630340.2

Allele description [Variation Report for NM_001754.5(RUNX1):c.145C>G (p.Pro49Ala)]

NM_001754.5(RUNX1):c.145C>G (p.Pro49Ala)

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.145C>G (p.Pro49Ala)
Other names:
NM_001754.5(RUNX1):c.145C>G; p.Pro49Ala
HGVS:
  • NC_000021.9:g.34887049G>C
  • NG_011402.2:g.1102663C>G
  • NG_144242.1:g.524G>C
  • NM_001001890.3:c.64C>G
  • NM_001122607.2:c.64C>G
  • NM_001754.5:c.145C>GMANE SELECT
  • NP_001001890.1:p.Pro22Ala
  • NP_001116079.1:p.Pro22Ala
  • NP_001745.2:p.Pro49Ala
  • NP_001745.2:p.Pro49Ala
  • LRG_482t1:c.145C>G
  • LRG_482:g.1102663C>G
  • LRG_482p1:p.Pro49Ala
  • NC_000021.8:g.36259346G>C
  • NM_001754.4:c.145C>G
Protein change:
P22A
Molecular consequence:
  • NM_001001890.3:c.64C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001122607.2:c.64C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001754.5:c.145C>G - missense variant - [Sequence Ontology: SO:0001583]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004407910Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 13, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

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, SCV004407910.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RUNX1-related conditions. This variant is present in population databases (rs755793721, gnomAD 0.002%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 49 of the RUNX1 protein (p.Pro49Ala).

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

Last Updated: Oct 8, 2024