Submissions for variant NM_001377.3(DYNC2H1):c.5793G>C (p.Leu1931Phe)

gnomAD frequency: 0.00013  dbSNP: rs185504536

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001093954	SCV000366713	uncertain significance	Asphyxiating thoracic dystrophy 3	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	RCV000381704	SCV000366714	uncertain significance	Short rib-polydactyly syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV001526643	SCV001737074	likely pathogenic	Neonatal respiratory distress		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001093954	SCV002048330	uncertain significance	Asphyxiating thoracic dystrophy 3	2023-09-12	criteria provided, single submitter	clinical testing	The DYNC2H1 c.5793G>C; p.Leu1931Phe variant (rs185504536) is reported in the literature in an individual affected with asphyxiating thoracic dystrophy but a second variant was not identified (Zhang 2018). This variant is found in the general population with an overall allele frequency of 0.016% (39/248,154 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL:0.13). Due to limited information, the clinical significance of the p.Leu1931Phe variant is uncertain at this time. References: Zhang et al. Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies. Hum Mutat. 2018 Jan;39(1):152-166. PMID: 29068549.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000345802	SCV002181688	likely benign	Jeune thoracic dystrophy	2024-01-29	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001093954	SCV003830801	uncertain significance	Asphyxiating thoracic dystrophy 3	2022-05-10	criteria provided, single submitter	clinical testing
Dan Cohn Lab, University Of California Los Angeles	RCV000345802	SCV000612109	uncertain significance	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000345802	SCV001479539	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research