Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001366207.1(DLG1):c.1898A>G(p.Asp633Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,612,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D633E) has been classified as Benign.
DLG1 (HGNC:2900): (discs large MAGUK scaffold protein 1) This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. A multitude of transcript variants deriving from alternative splicing and the use of multiple alternate promoter have been observed, including some splice variants that may be specific to brain and other tissues. An upstream uORF may regulate translation at some splice variants of this gene. [provided by RefSeq, Sep 2018]
Uncertain significance, criteria provided, single submitter
clinical testing
Ambry Genetics
Jan 18, 2022
The c.1997A>G (p.D666G) alteration is located in exon 18 (coding exon 17) of the DLG1 gene. This alteration results from a A to G substitution at nucleotide position 1997, causing the aspartic acid (D) at amino acid position 666 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -