Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000290773 | SCV000369311 | uncertain significance | Diabetes mellitus, transient neonatal, 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV000331715 | SCV000369312 | uncertain significance | Permanent neonatal diabetes mellitus | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV000386179 | SCV000369313 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Genetic Services Laboratory, |
RCV001820892 | SCV002065330 | uncertain significance | not specified | 2021-07-23 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the ABCC8 gene demonstrated a sequence change, c.2635G>A, in exon 22 that results in an amino acid change, p.Asp879Asn. This sequence change has been described in the gnomAD database with a frequency of 0.037% in the African/African-American subpopulation (dbSNP rs531684936). The p.Asp879Asn change affects a moderately conserved amino acid residue located in a domain of the ABCC8 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Asp879Asn substitution. This sequence change does not appear to have been previously described in individuals with ABCC8-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Asp879Asn change remains unknown at this time. |
Fulgent Genetics, |
RCV002480109 | SCV002789409 | uncertain significance | Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 | 2024-04-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002520699 | SCV003273202 | likely benign | not provided | 2024-01-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002520700 | SCV003638203 | uncertain significance | Inborn genetic diseases | 2022-07-30 | criteria provided, single submitter | clinical testing | The c.2635G>A (p.D879N) alteration is located in exon 22 (coding exon 22) of the ABCC8 gene. This alteration results from a G to A substitution at nucleotide position 2635, causing the aspartic acid (D) at amino acid position 879 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001820892 | SCV005394443 | uncertain significance | not specified | 2024-09-13 | criteria provided, single submitter | clinical testing | Variant summary: ABCC8 c.2635G>A (p.Asp879Asn) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251482 control chromosomes, predominantly at a frequency of 0.00037 within the African or African-American subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2635G>A has been reported in the literature in one individual affected with permanenent neonatal diabetes mellitus, co-occurring with a de novo pathogenic variant in ABCC8 (L225P) (Masia_2007). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hyperinsulinism. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 17317760). ClinVar contains an entry for this variant (Variation ID: 303771). Based on the evidence outlined above, the variant was classified as uncertain significance. |