Submissions for variant NM_006096.4(NDRG1):c.31G>A (p.Ala11Thr)

gnomAD frequency: 0.00140  dbSNP: rs145871479

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083085	SCV000261903	likely benign	Charcot-Marie-Tooth disease type 4	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000710163	SCV000292635	likely benign	not provided	2021-03-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32376792)
Athena Diagnostics	RCV000710163	SCV000614152	likely benign	not provided	2019-11-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001162095	SCV000884217	uncertain significance	Charcot-Marie-Tooth disease type 4D	2023-09-22	criteria provided, single submitter	clinical testing	The NDRG1 c.31G>A; p.Ala11Thr variant (rs145871479) is reported in the literature in a cohort of CMT patients (Volodarsky 2021), and is also reported in ClinVar (Variation ID: 220934). This variant is observed in the general population with an overall allele frequency of 0.1% (313/282870 alleles, including 1 homozygote) in the Genome Aggregation Database. The alanine at codon 11 is weakly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.153). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Volodarsky M et al. Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients. J Med Genet. 2021 Apr;58(4):284-288. PMID: 32376792.
Illumina Laboratory Services, Illumina	RCV001162095	SCV001324030	uncertain significance	Charcot-Marie-Tooth disease type 4D	2018-01-12	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.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173729	SCV001336843	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000710163	SCV001500524	uncertain significance	not provided	2020-11-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000710163	SCV001716005	uncertain significance	not provided	2022-11-25	criteria provided, single submitter	clinical testing	BP4
Ambry Genetics	RCV002321816	SCV002609143	uncertain significance	Inborn genetic diseases	2023-12-20	criteria provided, single submitter	clinical testing	The c.31G>A (p.A11T) alteration is located in exon 2 (coding exon 1) of the NDRG1 gene. This alteration results from a G to A substitution at nucleotide position 31, causing the alanine (A) at amino acid position 11 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003417751	SCV004118153	uncertain significance	NDRG1-related disorder	2023-04-21	criteria provided, single submitter	clinical testing	The NDRG1 c.31G>A variant is predicted to result in the amino acid substitution p.Ala11Thr. This variant was reported in an individual with Charcot-Marie-Tooth disease (Table S2, Volodarsky et al 2021. PubMed ID: 32376792). This variant is reported in 0.23% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-134296524-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc.	RCV001083085	SCV001456524	likely benign	Charcot-Marie-Tooth disease type 4	2019-12-27	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000710163	SCV001977909	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000710163	SCV001978759	likely benign	not provided		no assertion criteria provided	clinical testing