Submissions for variant NM_000263.4(NAGLU):c.9GGTGGC[3] (p.4VA[3])

dbSNP: rs1024697806

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000652885	SCV000774757	likely benign	Mucopolysaccharidosis, MPS-III-B; Charcot-Marie-Tooth disease axonal type 2V	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001090844	SCV001246597	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001331106	SCV001523047	uncertain significance	Mucopolysaccharidosis, MPS-III-B	2019-03-27	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001824856	SCV002074491	likely benign	not specified	2022-01-31	criteria provided, single submitter	clinical testing	Variant summary: NAGLU c.15_20dupGGTGGC (p.Val6_Ala7dup) results in an in-frame duplication that is predicted to duplicate two amino acids into the encoded protein. The variant allele was found at a frequency of 0.00077 in 31166 control chromosomes, predominantly at a frequency of 0.0028 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.12 fold of the estimated maximal expected allele frequency for a pathogenic variant in NAGLU causing Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) phenotype (0.0025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.15_20dupGGTGGC in individuals affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One lab classified as likely benign while two classified as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003937989	SCV004758754	likely benign	NAGLU-related condition	2023-01-31	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).