NM_001754.5(RUNX1):c.*2768A>C AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Germline classification:: Benign (2 submissions)
Last evaluated:: Jan 13, 2020
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:: RCV000278568.6

Allele description [Variation Report for NM_001754.5(RUNX1):c.*2768A>C]

NM_001754.5(RUNX1):c.*2768A>C

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.*2768A>C

HGVS:

NC_000021.9:g.34789367T>G
NG_011402.2:g.1200345A>C
NM_001001890.3:c.*2768A>C
NM_001754.5:c.*2768A>CMANE SELECT
LRG_482t1:c.*2768A>C
LRG_482:g.1200345A>C
NC_000021.8:g.36161664T>G
NM_001754.4(RUNX1):c.*2768A>C
NM_001754.4:c.*2768A>C

Links:

dbSNP: rs74950917

NCBI 1000 Genomes Browser:

rs74950917

Molecular consequence:

NM_001001890.3:c.*2768A>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001754.5:c.*2768A>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000435887	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV001244337	ClinGen Myeloid Malignancy Variant Curation Expert Panel	reviewed by expert panel (ClinGen MyeloMalig ACMG Specifications v1)	Benign (Jan 13, 2020)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000435887

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV001244337

ClinGen Myeloid Malignancy Variant Curation Expert Panel

reviewed by expert panel

(ClinGen MyeloMalig ACMG Specifications v1)

Benign
(Jan 13, 2020)

germline

curation

Citation Link

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, curation

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000435887.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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 ClinGen Myeloid Malignancy Variant Curation Expert Panel, SCV001244337.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The NM_001754.4(RUNX1):c.*2768A>C variant in the 3' UTR has an MAF of 0.0935 (9%, 3917/41896 alleles) in the African subpopulation of the gnomAD v3 cohort and is =/> 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in 167 individuals in the gnomAD v3 population database (BP2). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP2.

#	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

Last Updated: Dec 24, 2023

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