ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.2695-1G>C

gnomAD frequency: 0.00001  dbSNP: rs1057517420
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588002 SCV000696586 pathogenic Familial hyperinsulinism 2016-12-01 criteria provided, single submitter clinical testing Variant summary: The ABCC8 c.2695-1G>C variant involves the alteration of a conserved intronic nucleotide, at a position known to affect splicing, which 5/5 splice prediction tools predict the loss of a splice site, although these predictions have yet to be functionally assessed. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and a publication indicates the variant was observed in one child diagnosed with Congenital Hyperinsulinism. A database has cited the variant as a disease causing mutation. Therefore, the variant of interest has been classified as Pathogenic.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002251474 SCV002522127 uncertain significance Maturity onset diabetes mellitus in young 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 have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs1057517420) in MODY yet.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002251475 SCV002522128 uncertain significance 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 have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs1057517420) in neonatal diabetes yet.
Labcorp Genetics (formerly Invitae), Labcorp RCV002523883 SCV003440250 pathogenic not provided 2023-02-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 371626). This variant is also known as c.2698-1G>C. Disruption of this splice site has been observed in individuals with autosomal recessive congenital hyperinsulinism (PMID: 23275527). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 22 of the ABCC8 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ABCC8 are known to be pathogenic (PMID: 20685672, 23345197).
Baylor Genetics RCV003470354 SCV004197062 pathogenic Type 2 diabetes mellitus 2023-08-20 criteria provided, single submitter clinical testing
Counsyl RCV000409858 SCV000487252 likely pathogenic Hyperinsulinemic hypoglycemia, familial, 1 2016-11-02 no assertion criteria provided clinical testing

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