Submissions for variant NM_138477.4(CDAN1):c.2029C>T (p.Arg677Trp)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University of Leipzig Medical Center	RCV002286499	SCV002576472	uncertain significance	Anemia, congenital dyserythropoietic, type 1a	2022-09-20	criteria provided, single submitter	clinical testing	This variant was identified as compound heterozygous with NM_138477.4:c.2110G>A._x000D_ Criteria applied: PP3, PM2_SUP, PM3_SUP
Revvity Omics, Revvity	RCV002286499	SCV003829400	uncertain significance	Anemia, congenital dyserythropoietic, type 1a	2023-10-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235699	SCV003934191	uncertain significance	not specified	2023-05-23	criteria provided, single submitter	clinical testing	Variant summary: CDAN1 c.2029C>T (p.Arg677Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5e-05 in 240710 control chromosomes (gnomAD). c.2029C>T has been reported in the literature in an individual affected with Congenital dyserythropoietic anemia (Wang_2018), and this patient was reported as compound heterozygous with a truncating variant. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29031773). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV002286499	SCV005402423	uncertain significance	Anemia, congenital dyserythropoietic, type 1a	2024-05-29	criteria provided, single submitter	clinical testing	The CDAN1 c.2029C>T (p.Arg677Trp) missense change has a maximum subpopulation frequency of 0.011% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge, functional studies have not been performed. This variant has been reported in the compound heterozygote state with V140fs in one individual with congenital dyserythropoietic anemia (PMID: 29031773). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.