U.S. flag

An official website of the United States government

NM_000352.6(ABCC8):c.579+2T>A AND Hyperinsulinemic hypoglycemia, familial, 1

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Aug 16, 2023
Review status:
criteria provided, conflicting classifications
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:
RCV000671080.4

Allele description [Variation Report for NM_000352.6(ABCC8):c.579+2T>A]

NM_000352.6(ABCC8):c.579+2T>A

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.579+2T>A
HGVS:
  • NC_000011.10:g.17463436A>T
  • NG_008867.1:g.18467T>A
  • NM_000352.6:c.579+2T>AMANE SELECT
  • NM_001287174.3:c.579+2T>A
  • NM_001351295.2:c.579+2T>A
  • NM_001351296.2:c.579+2T>A
  • NM_001351297.2:c.579+2T>A
  • LRG_790t1:c.579+2T>A
  • LRG_790t2:c.579+2T>A
  • LRG_790:g.18467T>A
  • NC_000011.9:g.17484983A>T
  • NM_000352.3:c.579+2T>A
Links:
dbSNP: rs1449198328
NCBI 1000 Genomes Browser:
rs1449198328
Molecular consequence:
  • NM_000352.6:c.579+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001287174.3:c.579+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001351295.2:c.579+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001351296.2:c.579+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001351297.2:c.579+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hyperinsulinemic hypoglycemia, familial, 1 (HHF1)
Synonyms:
HYPERINSULINISM, FAMILIAL, WITH PANCREATIC NESIDIOBLASTOSIS; HYPOGLYCEMIA, HYPERINSULINEMIC, OF INFANCY; NESIDIOBLASTOSIS OF PANCREAS; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009734; MedGen: C2931832; Orphanet: 276575; Orphanet: 276598; OMIM: 256450

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000796022Counsyl
criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))		Likely pathogenic
(Nov 30, 2017) 		unknownclinical testing

Citation Link,

SCV004026599Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 16, 2023) 		germlinecuration

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Counsyl, SCV000796022.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV004026599.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The c.579+2T>A variant in ABCC8 has not been previously reported in the literature in individuals with hyperinsulinemic hypoglycemia, but has been identified in 0.003% (1/32402) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1449198328). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (VariationID: 555287) and has been interpreted as likely pathogenic by Counsyl. This variant is located in the 3' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. There is an in-frame cryptic splice site 6 bases from the intron-exon boundary, providing evidence that this variant may delete 2 amino acids instead of causing loss of function. However, this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the c.579+2T>A variant is uncertain. ACMG/AMP Criteria applied: PVS1_strong, PM2_supporting (Richards 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 13, 2025