ClinVar Miner

Submissions for variant NM_001987.5(ETV6):c.632G>A (p.Arg211His)

gnomAD frequency: 0.00004  dbSNP: rs111871763
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV001281685 SCV001469033 uncertain significance Thrombocytopenia 5 2020-12-11 criteria provided, single submitter clinical testing This ETV6 variant has been reported in both an individual presenting with myelodysplastic syndrome and idiopathic cytopenia of undetermined significance. ETV6 c.632G>A (rs111871763) is rare (<0.1%) in a large population dataset (gnomAD: 10/282746 total alleles; 0.004%; no homozygotes) and has not been reported in ClinVar nor the literature, to our knowledge. Three bioinformatic tools queried predict that this substitution would be tolerated, and the arginine residue at this position is evolutionarily conserved across mammals. We consider the clinical significance of c.632G>A to be uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV002537925 SCV003470101 uncertain significance not provided 2023-01-15 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ETV6 protein function. ClinVar contains an entry for this variant (Variation ID: 992913). This missense change has been observed in individual(s) with acute lymphoblastic leukaemia (PMID: 26522332). This variant is present in population databases (rs111871763, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 211 of the ETV6 protein (p.Arg211His).
GeneDx RCV002537925 SCV005372013 uncertain significance not provided 2023-07-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in a patient with childhood acute lymphoblastic leukemia (PMID: 26522332); This variant is associated with the following publications: (PMID: 33179473, 17988997, 26522332)
Ambry Genetics RCV004978240 SCV005584997 likely benign Inborn genetic diseases 2024-10-17 criteria provided, single submitter clinical testing This alteration is classified as likely 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.

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