NM_000352.6(ABCC8):c.1333-1013A>G AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 10, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001211946.7

Allele description [Variation Report for NM_000352.6(ABCC8):c.1333-1013A>G]

NM_000352.6(ABCC8):c.1333-1013A>G

Gene:

ABCC8:ATP binding cassette subfamily C member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000352.6(ABCC8):c.1333-1013A>G

HGVS:

NC_000011.10:g.17444325T>C
NG_008867.1:g.37578A>G
NM_000352.6:c.1333-1013A>GMANE SELECT
NM_001287174.3:c.1333-1013A>G
NM_001351295.2:c.1333-1013A>G
NM_001351296.2:c.1330-1013A>G
NM_001351297.2:c.1330-1013A>G
LRG_790t1:c.1333-1013A>G
LRG_790t2:c.1333-1013A>G
LRG_790:g.37578A>G
NC_000011.9:g.17465872T>C
NM_000352.3:c.1333-1013A>G
NM_000352.4:c.1333-1013A>G

Nucleotide change:

IVS8, A-G, -1013

Links:

OMIM: 600509.0029; dbSNP: rs980458021

NCBI 1000 Genomes Browser:

rs980458021

Molecular consequence:

NM_000352.6:c.1333-1013A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001287174.3:c.1333-1013A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351295.2:c.1333-1013A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351296.2:c.1330-1013A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351297.2:c.1330-1013A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001383514	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 10, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23273570, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001383514

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 10, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.

Flanagan SE, Xie W, Caswell R, Damhuis A, Vianey-Saban C, Akcay T, Darendeliler F, Bas F, Guven A, Siklar Z, Ocal G, Berberoglu M, Murphy N, O'Sullivan M, Green A, Clayton PE, Banerjee I, Clayton PT, Hussain K, Weedon MN, Ellard S.

Am J Hum Genet. 2013 Jan 10;92(1):131-6. doi: 10.1016/j.ajhg.2012.11.017. Epub 2012 Dec 27.

PubMed [citation]

PMID:: 23273570
PMCID:: PMC3542457

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001383514.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change falls in intron 8 of the ABCC8 gene. It does not directly change the encoded amino acid sequence of the ABCC8 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with autosomal recessive diffuse or focal hyperinsulinism (PMID: 23273570). ClinVar contains an entry for this variant (Variation ID: 39472). Studies have shown that this variant results in inclusion of 76 nucleotides from intron 8 and introduces a premature termination codon (PMID: 23273570). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2025

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