ClinVar Miner

Submissions for variant NM_018965.4(TREM2):c.377T>G (p.Val126Gly)

gnomAD frequency: 0.00001  dbSNP: rs121908402
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000721926 SCV001146848 likely pathogenic Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 2019-10-17 criteria provided, single submitter curation This variant is interpreted as Likely pathogenic for Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 , autosomal recessive. The following ACMG Tag(s) were applied: PM2, PP3, PM3, PS3.
PreventionGenetics, part of Exact Sciences RCV003398447 SCV004111781 pathogenic TREM2-related disorder 2022-12-14 criteria provided, single submitter clinical testing The TREM2 c.377T>G variant is predicted to result in the amino acid substitution p.Val126Gly. This variant has been reported in individuals with Nasu-Hakola disease, also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (Klünemann et al 2005. PubMed ID: 15883308; Lynch DS et al 2017. PubMed ID: 28334938). Functional studies showed the p.Val126Gly change disrupts TREM2 trafficking to the cell membrane and impairs function (Sirkis DW et al 2017. PubMed ID: 28768830; Kober DL et al 2016. PubMed ID: 27995897). This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-41129015-A-C).This variant is interpreted as pathogenic.
OMIM RCV000721926 SCV000025710 pathogenic Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 2005-05-10 no assertion criteria provided literature only
GeneReviews RCV000005528 SCV000223800 not provided Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 no assertion provided literature only

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