NM_001754.5(RUNX1):c.749G>A (p.Arg250His) AND Acute myeloid leukemia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001255168.3

Allele description [Variation Report for NM_001754.5(RUNX1):c.749G>A (p.Arg250His)]

NM_001754.5(RUNX1):c.749G>A (p.Arg250His)

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.749G>A (p.Arg250His)

Other names:

NM_001754.5(RUNX1):c.749G>A

HGVS:

NC_000021.9:g.34834466C>T
NG_011402.2:g.1155246G>A
NM_001001890.3:c.668G>A
NM_001122607.2:c.668G>A
NM_001754.5:c.749G>AMANE SELECT
NP_001001890.1:p.Arg223His
NP_001116079.1:p.Arg223His
NP_001745.2:p.Arg250His
NP_001745.2:p.Arg250His
LRG_482t1:c.749G>A
LRG_482:g.1155246G>A
LRG_482p1:p.Arg250His
NC_000021.8:g.36206763C>T
NM_001754.4:c.749G>A

Protein change:

R223H

Links:

dbSNP: rs771614642

NCBI 1000 Genomes Browser:

rs771614642

Molecular consequence:

NM_001001890.3:c.668G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001122607.2:c.668G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001754.5:c.749G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Acute myeloid leukemia (AML)
Synonyms:: Acute myeloid leukemia, adult; AML adult; Acute myelogenous leukemia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018874; MeSH: D015470; MedGen: C0023467; Orphanet: 519; OMIM: 601626; Human Phenotype Ontology: HP:0004808

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001431517	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 17, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004209865	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 1, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001431517

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 17, 2020)

germline

clinical testing

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

SCV004209865

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 1, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV001431517.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This RUNX1 variant (rs771614642) is rare (<0.1%) in a large population dataset (gnomAD: 11/281252 total alleles; 0.004%; no homozygotes) and has not been reported in the literature, to our knowledge. RUNX1 c.749G>A has been reported in ClinVar. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the other predicts that it would be tolerated. Due to insufficient evidence, we consider its clinical significance uncertain at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004209865.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine