ClinVar Miner

Submissions for variant NM_006363.6(SEC23B):c.1571C>T (p.Ala524Val)

gnomAD frequency: 0.00001  dbSNP: rs398124225
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000081403 SCV000113334 pathogenic not provided 2013-11-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003764767 SCV004568808 likely pathogenic Congenital dyserythropoietic anemia, type II; Cowden syndrome 7 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 524 of the SEC23B protein (p.Ala524Val). This variant is present in population databases (rs398124225, gnomAD 0.02%). This missense change has been observed in individuals with congenital dyserythropoietic anemia type II (PMID: 19561605, 20015893, 30747246). ClinVar contains an entry for this variant (Variation ID: 95384). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SEC23B protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001843475 SCV005418411 likely pathogenic Congenital dyserythropoietic anemia, type II criteria provided, single submitter clinical testing PM2_Supporting+PP3+PM3_Strong
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001843475 SCV005887538 pathogenic Congenital dyserythropoietic anemia, type II 2025-01-24 criteria provided, single submitter clinical testing Variant summary: SEC23B c.1571C>T (p.Ala524Val) results in a non-conservative amino acid change located in the Sec23/Sec24, helical domain (IPR006900) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251468 control chromosomes (gnomAD). c.1571C>T has been reported in the literature in multiple individuals affected with Congenital dyserythropoietic anemia, type II and this variant co-segregated with the disease (Schwarz_2009, Iolascon_2009, Zhang_2019, Feng_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34365611, 20015893, 21850656, 19561605, 30747246). ClinVar contains an entry for this variant (Variation ID: 95384). Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Human Genetics, Heidelberg University RCV001843475 SCV002102983 likely pathogenic Congenital dyserythropoietic anemia, type II 2021-10-22 no assertion criteria provided clinical testing

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