Submissions for variant NM_001378120.1(MBD5):c.3743A>G (p.Gln1248Arg)

gnomAD frequency: 0.00068  dbSNP: rs143028540

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174142	SCV000225388	benign	not specified	2014-06-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000514989	SCV000241712	likely benign	not provided	2021-03-17	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514989	SCV000610602	likely benign	not provided	2017-02-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079154	SCV000645799	likely benign	Intellectual disability, autosomal dominant 1	2025-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002317001	SCV000850292	likely benign	Inborn genetic diseases	2017-12-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000514989	SCV001500228	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	MBD5: BS1
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001079154	SCV003924121	likely benign	Intellectual disability, autosomal dominant 1	2021-03-30	criteria provided, single submitter	clinical testing	MBD5 NM_018328.4 exon 11 p.Gln1015Arg (c.3044A>G): This variant has not been reported in the literature but is present in 0.1% (78/64570) of European alleles in the Genome Aggregation Database, including 1 homozygote (https://gnomad.broadinstitute.org/variant/2-148485940-A-G?dataset=gnomad_r3). This variant is also present in ClinVar, with several labs classifying this variant as benign or likely benign (Variation ID:193911). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003937556	SCV004750222	likely benign	MBD5-related disorder	2022-09-15	no assertion criteria provided	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).