Submissions for variant NM_001987.5(ETV6):c.380G>A (p.Arg127Gln)

gnomAD frequency: 0.00068  dbSNP: rs140357643

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV001336416	SCV001529794	uncertain significance	Thrombocytopenia 5	2018-09-28	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. It was reported as a germline variant of unknown significance in one individual with chronic myeloid leukemia [PMID 29365323]
GeneDx	RCV001572489	SCV001797142	likely benign	not provided	2020-12-22	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with chronic myelomonocytic leukemia (Drazer 2018); This variant is associated with the following publications: (PMID: 29365323, 12210491)
Genetic Services Laboratory, University of Chicago	RCV001820033	SCV002064927	uncertain significance	not specified	2021-08-11	criteria provided, single submitter	clinical testing	DNA sequence analysis of the ETV6 gene demonstrated a sequence change, c.380G>A, in exon 4 that results in an amino acid change, p.Arg127Gln. This sequence change has been described in the gnomAD database with a frequency of 0.11% in the European (non-Finnish) subpopulation (dbSNP rs140357643). The p.Arg127Gln change affects a highly conserved amino acid residue located in a domain of the ETV6 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg127Gln substitution. This sequence change has been reported as a variant of uncertain significance in an individual with chronic myelogenous leukemia in both tumor tissue and germline tissue (PMID: 293653230). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Arg127Gln change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001572489	SCV003255846	likely benign	not provided	2025-01-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004978352	SCV005584996	benign	Inborn genetic diseases	2024-07-30	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003963228	SCV004779594	likely benign	ETV6-related disorder	2022-03-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).