ClinVar Miner

Submissions for variant NM_006852.6(TLK2):c.1636C>T (p.Arg546Trp)

gnomAD frequency: 0.00001  dbSNP: rs1283838287
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000755743 SCV000883263 likely pathogenic Intellectual disability, autosomal dominant 57 2018-10-15 criteria provided, single submitter curation This variant is interpreted as Likely Pathogenic, for Mental retardation, autosomal dominant 57. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6 => Assumed de novo, but without confirmation of paternity and maternity (https://www.ncbi.nlm.nih.gov/pubmed/29861108). PM1 => Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (https://www.uniprot.org/uniprot/Q86UE8).
3billion, Medical Genetics RCV000755743 SCV002012035 pathogenic Intellectual disability, autosomal dominant 57 2021-10-02 criteria provided, single submitter clinical testing The variant has been previously reported as de novoo in a similarly affected individual (PMID: 29861108, PS2). The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1).The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000319, PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (3Cnet: 0.669, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV002293477 SCV002586598 pathogenic not provided 2024-12-23 criteria provided, single submitter clinical testing 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: 29861108, 29758565, 34821460)

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