ClinVar Miner

Submissions for variant NM_145207.3(AFG2A):c.1964G>A (p.Arg655Gln)

gnomAD frequency: 0.00058  dbSNP: rs147873489
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000713497 SCV000238566 likely pathogenic not provided 2024-09-26 criteria provided, single submitter clinical testing Observed in homozygous state in a patient with white matter disease in the literature (PMID: 35012964); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35012964)
Labcorp Genetics (formerly Invitae), Labcorp RCV000527650 SCV000655989 uncertain significance Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 655 of the SPATA5 protein (p.Arg655Gln). This variant is present in population databases (rs147873489, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SPATA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 203526). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Eurofins Ntd Llc (ga) RCV000713497 SCV000702790 uncertain significance not provided 2016-10-17 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000713497 SCV000844116 uncertain significance not provided 2018-01-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000527650 SCV000895617 uncertain significance Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome 2018-10-31 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000527650 SCV002759341 uncertain significance Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome 2022-12-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004525890 SCV005039429 uncertain significance not specified 2024-03-12 criteria provided, single submitter clinical testing Variant summary: SPATA5 c.1964G>A (p.Arg655Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00058 in 251440 control chromosomes (gnomAD). c.1964G>A has been reported in the literature in an individual affected with white matter disorder (Schluter_2022). This report does not provide unequivocal conclusions about association of the variant with Epilepsy, Hearing Loss, And Mental Retardation Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35012964). ClinVar contains an entry for this variant (Variation ID: 203526). Based on the evidence outlined above, the variant was classified as uncertain significance.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005361093 SCV005915113 uncertain significance Syndromic complex neurodevelopmental disorder 2022-12-05 criteria provided, single submitter research

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