Submissions for variant NM_001377.3(DYNC2H1):c.5821G>C (p.Ala1941Pro)

gnomAD frequency: 0.00006  dbSNP: rs368058473

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723912	SCV000202639	uncertain significance	not provided	2014-04-27	criteria provided, single submitter	clinical testing
Invitae	RCV000167972	SCV000218620	uncertain significance	Jeune thoracic dystrophy	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1941 of the DYNC2H1 protein (p.Ala1941Pro). This variant is present in population databases (rs368058473, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 167012). 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 DYNC2H1 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.
GeneDx	RCV000723912	SCV000517476	uncertain significance	not provided	2022-12-22	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Observed with a likely pathogenic variant on the opposite allele (in trans) in a patient referred for genetic testing at GeneDx with clinical features suggestive of a skeletal dysplasia
Genetic Services Laboratory, University of Chicago	RCV001818345	SCV002069618	uncertain significance	not specified	2019-09-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003278673	SCV004006895	uncertain significance	Inborn genetic diseases	2023-05-31	criteria provided, single submitter	clinical testing	The c.5821G>C (p.A1941P) alteration is located in exon 37 (coding exon 37) of the DYNC2H1 gene. This alteration results from a G to C substitution at nucleotide position 5821, causing the alanine (A) at amino acid position 1941 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003407576	SCV004113123	uncertain significance	DYNC2H1-related condition	2022-12-21	criteria provided, single submitter	clinical testing	The DYNC2H1 c.5821G>C variant is predicted to result in the amino acid substitution p.Ala1941Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-103047110-G-C). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.