Submissions for variant NM_001083614.2(EARS2):c.263C>A (p.Ala88Glu)

gnomAD frequency: 0.00118  dbSNP: rs201929423

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000314264	SCV000396068	uncertain significance	Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome	2018-01-12	criteria provided, single submitter	clinical testing	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000906961	SCV001051632	likely benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000314264	SCV001529486	uncertain significance	Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome	2018-09-19	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV000906961	SCV003805518	uncertain significance	not provided	2023-02-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified as heterozygous in a patient with infantile respiratory chain deficiency who was also homoplasmic for the m.14674 T>C pathogenic variant in the MT-TE gene (Hathazi et al., 2020); This variant is associated with the following publications: (PMID: 33128823)
CeGaT Center for Human Genetics Tuebingen	RCV000906961	SCV004700503	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000906961	SCV005411272	uncertain significance	not provided	2023-09-25	criteria provided, single submitter	clinical testing	BS1
PreventionGenetics, part of Exact Sciences	RCV004549700	SCV004770620	likely benign	EARS2-related disorder	2022-05-09	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).