Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001077415.3(CRELD1):c.232G>C(p.Glu78Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,474 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. E78D) has been classified as Uncertain significance.
CRELD1 (HGNC:14630): (cysteine rich with EGF like domains 1) This gene encodes a member of a subfamily of epidermal growth factor-related proteins. The encoded protein is characterized by a cysteine-rich with epidermal growth factor-like domain. This protein may function as a cell adhesion molecule. Mutations in this gene are the cause of atrioventricular septal defect. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.3164981).
Uncertain significance, criteria provided, single submitter
clinical testing
GeneDx
Jan 11, 2022
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Gain of glycosylation at T73 (P = 0.0513);Gain of glycosylation at T73 (P = 0.0513);Gain of glycosylation at T73 (P = 0.0513);Gain of glycosylation at T73 (P = 0.0513);