NM_001754.5(RUNX1):c.447A>C (p.Ala149=) AND Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 6, 2022
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:: RCV002264807.2

Allele description [Variation Report for NM_001754.5(RUNX1):c.447A>C (p.Ala149=)]

NM_001754.5(RUNX1):c.447A>C (p.Ala149=)

Genes:

RUNX1:RUNX family transcription factor 1 [Gene - OMIM - HGNC]
RUNX1-AS1:RUNX1 antisense RNA 1 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.12

Genomic location:

Preferred name:

NM_001754.5(RUNX1):c.447A>C (p.Ala149=)

Other names:

NM_001754.5(RUNX1):c.447A>C; p.Ala149=

HGVS:

NC_000021.9:g.34880618T>G
NG_011402.2:g.1109094A>C
NM_001001890.3:c.366A>C
NM_001122607.2:c.366A>C
NM_001754.5:c.447A>CMANE SELECT
NP_001001890.1:p.Ala122=
NP_001116079.1:p.Ala122=
NP_001745.2:p.Ala149=
LRG_482:g.1109094A>C
NC_000021.8:g.36252915T>G

Links:

dbSNP: rs1383915216

NCBI 1000 Genomes Browser:

rs1383915216

Molecular consequence:

NM_001001890.3:c.366A>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001122607.2:c.366A>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001754.5:c.447A>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Identifiers:: MONDO: MONDO:0011071; MedGen: CN281654

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002546472	ClinGen Myeloid Malignancy Variant Curation Expert Panel	reviewed by expert panel (ClinGen MyeloMalig ACMG Specifications v2)	Uncertain significance (Jul 6, 2022)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002546472

ClinGen Myeloid Malignancy Variant Curation Expert Panel

reviewed by expert panel

(ClinGen MyeloMalig ACMG Specifications v2)

Uncertain significance
(Jul 6, 2022)

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	curation

Details of each submission

From ClinGen Myeloid Malignancy Variant Curation Expert Panel, SCV002546472.1

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

Description

NM_001754.5(RUNX1):c.447A>C (p.Ala149=) is a synonymous variant. No REVEL score because a synonymous variant and SpliceAI is ≤0.20 (BP4). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets the criteria to be classified as a variant of Uncertain significance - insufficient evidence. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and PM2_supporting.

#	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: Sep 29, 2024

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