ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.2169_2171del (p.Leu724del)

dbSNP: rs760520781
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NxGen MDx RCV001353384 SCV001548542 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2020-01-27 criteria provided, single submitter clinical testing This in-frame deletion (c.2169_2171del) in ABCC8 results in the loss of 1 of 3 repeated leucine residues (p.Leu724del) in the ABC transporter 1 domain (PM1). This variant has a very low allele frequency in gnomAD exomes (PM2) and has been reported by Mohnike et al. PMID 24401662 in one patient with preterm birth and diffuse histology, requiring a pancreatectomy. The authors also used two in silico models to predict this variant as pathogenic (PP3). This variant was also reported in Xu et al. PMID 31208162 in conjunction with a frameshift (c.817del , p.Gln273Argfsx85 ) in a neonate affected with congenital hyperinsulinism(CHI) . We interpret c.2169_2171del to be likely pathogenic.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV001353384 SCV002522251 uncertain risk allele Hyperinsulinemic hypoglycemia, familial, 1 2024-05-27 criteria provided, single submitter research This variant is found to be a potent moderate impact, with a CADD score of 6.23 and sufficient scientific evidence to support gene-disease correlation. This is found more frequently in congenital Hyperinsulinism cases as per recent evidence as well. However, since this is not a high impact variant and has limited evidence, this variant is reclassified as Uncertain risk allele only.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV004556839 SCV002522253 uncertain risk allele Neonatal diabetes mellitus 2024-05-27 criteria provided, single submitter research This variant is found to be a potent moderate impact, variant with a CADD score of 6.32 and sufficient scientific evidence of gene-disease correlation. However, since this is not a high impact variant and no variant evidence, this variant is reclassified as Uncertain risk allele.
3billion, Medical Genetics RCV001353384 SCV002573176 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2022-09-01 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Inframe deletion located in a nonrepeat region is predicted to change the length of the protein and disrupt normal protein function. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 31208162). The variant has been reported to be associated with ABCC8-related disorder (ClinVar ID: VCV001048785 / PMID: 23275527). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV003473877 SCV004203028 likely pathogenic Type 2 diabetes mellitus 2022-10-20 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.