Submissions for variant NM_015214.3(DDHD2):c.1130C>T (p.Ser377Leu)

gnomAD frequency: 0.00036  dbSNP: rs145943165

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000799863	SCV000939545	uncertain significance	Hereditary spastic paraplegia 54	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 377 of the DDHD2 protein (p.Ser377Leu). This variant is present in population databases (rs145943165, 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 DDHD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 645719). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DDHD2 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.
CeGaT Center for Human Genetics Tuebingen	RCV001532613	SCV001748250	uncertain significance	not provided	2024-06-01	criteria provided, single submitter	clinical testing	DDHD2: PM2, BP4
Genetic Services Laboratory, University of Chicago	RCV001816858	SCV002066423	uncertain significance	not specified	2019-04-16	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001849103	SCV002104600	uncertain significance	Hereditary spastic paraplegia	2020-08-14	criteria provided, single submitter	clinical testing