Submissions for variant NM_000352.6(ABCC8):c.3329+6C>T

gnomAD frequency: 0.01304  dbSNP: rs113873225

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000144991	SCV000051900	benign	not specified	2018-09-06	criteria provided, single submitter	clinical testing	Variant summary: ABCC8 c.3329+6C>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. 5/5 computational 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 0.012 in 274898 control chromosomes in the gnomAD database, including 26 homozygotes. The observed variant frequency is approximately 557705.035 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCC8 causing Neonatal Diabetes Mellitus phenotype (2.1e-08), strongly suggesting that the variant is benign. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Eurofins Ntd Llc (ga)	RCV000144991	SCV000228302	benign	not specified	2015-01-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000144991	SCV000303803	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000376345	SCV000369290	likely benign	Diabetes mellitus, transient neonatal, 2	2018-03-08	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000286774	SCV000369291	likely benign	Permanent neonatal diabetes mellitus	2018-03-08	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000323116	SCV000369292	likely benign	Hyperinsulinemic hypoglycemia, familial, 1	2018-03-08	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001512800	SCV001720265	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001512800	SCV001873458	benign	not provided	2020-02-27	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23652837)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226655	SCV002505497	benign	Transitory neonatal diabetes mellitus		criteria provided, single submitter	research	Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may respond to sulfonylureas. However, no sufficient evidence is found to ascertain the role of rs113873225 variant in Diabetes Mellitus yet.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001512800	SCV003799971	benign	not provided	2023-11-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001512800	SCV004136029	benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	ABCC8: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV001512800	SCV005221365	likely benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000144991	SCV000192027	likely benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001277192	SCV001464090	benign	Hereditary hyperinsulinism	2020-09-16	no assertion criteria provided	clinical testing