ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.2041-12C>T

dbSNP: rs201419039
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000353291 SCV000369347 benign Diabetes mellitus, transient neonatal, 2 2018-01-12 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000260794 SCV000369348 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2018-01-12 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, Illumina RCV000318223 SCV000369349 uncertain significance Permanent neonatal diabetes mellitus 2018-01-12 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.
Athena Diagnostics RCV000517738 SCV000612203 uncertain significance not specified 2016-08-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001414351 SCV001616484 likely benign not provided 2024-01-31 criteria provided, single submitter clinical testing
GeneDx RCV001414351 SCV001995955 uncertain significance not provided 2019-09-20 criteria provided, single submitter clinical testing In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000517738 SCV003800736 likely benign not specified 2023-01-10 criteria provided, single submitter clinical testing Variant summary: ABCC8 c.2041-12C>T 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. 4/4 computational tools predict no significant impact on normal splicing. A minigene assay has reported no impact of splicing (Saint-Martin_2021). The variant allele was found at a frequency of 0.0005 in 247584 control chromosomes. Although one study reported the presence of this variant on the paternal allele of an individual reportedly affected with Congenital Hyperinsulinism (CHI) and classified this variant as likely benign based on the minigene splicing result, to our knowledge, no conclusive occurrence of c.2041-12C>T in individuals affected with Congenital Hyperinsulinism and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (B/LB, n=2; VUS, n=4). Based on the evidence outlined above, the variant was classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001414351 SCV004563391 likely benign not provided 2023-11-22 criteria provided, single submitter clinical testing
Natera, Inc. RCV001272234 SCV001454036 uncertain significance Hereditary hyperinsulinism 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004544510 SCV004779572 likely benign ABCC8-related disorder 2019-08-26 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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