Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000907859 | SCV000533284 | benign | not provided | 2019-08-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000907859 | SCV001052588 | benign | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002348239 | SCV002646014 | benign | Cardiovascular phenotype | 2019-03-15 | criteria provided, single submitter | clinical testing | This alteration is classified as 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, |
RCV003479117 | SCV004222983 | likely benign | not specified | 2023-11-20 | criteria provided, single submitter | clinical testing | Variant summary: ALPK3 c.4474G>A (p.Ala1492Thr) results in a non-conservative amino acid change located in the Immunoglobulin subtype 2 (IPR003598) of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00094 in 251012 control chromosomes, predominantly at a frequency of 0.013 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.84 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALPK3 causing Cardiomyopathy phenotype (0.0071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.4474G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign. Based on the evidence outlined above, the variant was classified as likely benign. |