ClinVar Miner

Submissions for variant NM_001276270.2(MBD4):c.1469G>A (p.Trp490Ter)

gnomAD frequency: 0.00003  dbSNP: rs897132425
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005101512 SCV005806537 pathogenic not provided 2024-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp496*) in the MBD4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MBD4 are known to be pathogenic (PMID: 30049810, 35460607). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MBD4-related conditions. ClinVar contains an entry for this variant (Variation ID: 3029610). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV005377618 SCV006028364 pathogenic Inborn genetic diseases 2024-12-20 criteria provided, single submitter clinical testing The p.W490* pathogenic mutation (also known as c.1469G>A), located in coding exon 6 of the MBD4 gene, results from a G to A substitution at nucleotide position 1469. This changes the amino acid from a tryptophan to a stop codon within coding exon 6. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
PreventionGenetics, part of Exact Sciences RCV003896710 SCV004713830 uncertain significance MBD4-related disorder 2023-10-26 no assertion criteria provided clinical testing The MBD4 c.1487G>A variant is predicted to result in premature protein termination (p.Trp496*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-129152015-C-T). Of note, loss of function variants in MBD4 have not conclusively been associated with disease. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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