ClinVar Miner

Submissions for variant NM_001173990.3(TMEM216):c.140T>C (p.Val47Ala)

gnomAD frequency: 0.00052  dbSNP: rs762918371
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000401686 SCV000344452 uncertain significance not provided 2018-06-13 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000291175 SCV000372626 uncertain significance Meckel syndrome, type 2 2018-01-13 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.
Illumina Laboratory Services, Illumina RCV000345935 SCV000372627 uncertain significance Joubert syndrome 2 2018-01-13 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.
Fulgent Genetics, Fulgent Genetics RCV001788191 SCV000894640 uncertain significance Joubert syndrome 2; Meckel syndrome, type 2 2024-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001240998 SCV001413987 uncertain significance Familial aplasia of the vermis 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 47 of the TMEM216 protein (p.Val47Ala). This variant is present in population databases (rs762918371, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of inherited retinal disorder (PMID: 32483926). ClinVar contains an entry for this variant (Variation ID: 289981). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
GeneDx RCV000401686 SCV001822544 likely benign not provided 2024-01-03 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004816515 SCV005070337 uncertain significance Retinal dystrophy 2023-01-01 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV000401686 SCV005191309 uncertain significance not provided criteria provided, single submitter not provided
Natera, Inc. RCV000345935 SCV001466354 uncertain significance Joubert syndrome 2 2020-04-14 no assertion criteria provided clinical testing

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