Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002215211 | SCV002362075 | benign | X-linked agammaglobulinemia with growth hormone deficiency | 2024-01-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004603161 | SCV005094745 | likely benign | Inborn genetic diseases | 2024-06-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700599 | SCV005202712 | benign | not specified | 2024-07-10 | criteria provided, single submitter | clinical testing | Variant summary: BTK c.1104A>G (p.Gly368Gly) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 183509 control chromosomes, predominantly at a frequency of 0.0011 within the South Asian subpopulation in the gnomAD database, including 10 hemizygotes. The occurrence in several hemizygotes suggests that this variant is likely not associated with a high penetrance, severe, early onset disease phenotype in hemizygous state. The variant, c.1104A>G, was listed to be found in a cohort of patients affected with (suspected) X-Linked Agammaglobulinemia (Rawat_2021), however no supportive evidence details were provided. This report does not provide unequivocal conclusions about association of the variant with X-Linked Agammaglobulinemia. 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: 33584693). ClinVar contains an entry for this variant (Variation ID: 1570224). Based on the evidence outlined above, the variant was classified as benign. |