rs199702708
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000352.6(ABCC8):βc.647G>Aβ(p.Arg216His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000793 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R216C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000352.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCC8 | NM_000352.6 | c.647G>A | p.Arg216His | missense_variant | 5/39 | ENST00000389817.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCC8 | ENST00000389817.8 | c.647G>A | p.Arg216His | missense_variant | 5/39 | 1 | NM_000352.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251482Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135914
GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47AN XY: 727248
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74320
ClinVar
Submissions by phenotype
Hereditary hyperinsulinism Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Type 2 diabetes mellitus;C0271714:Leucine-induced hypoglycemia;C1835887:Diabetes mellitus, transient neonatal, 2;C2931832:Hyperinsulinemic hypoglycemia, familial, 1;C5394303:Diabetes mellitus, permanent neonatal 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 07, 2021 | - - |
Hyperinsulinemic hypoglycemia, familial, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Oct 26, 2022 | The c.647G>A variant in ABCC8 has previously been reported in an individual with hyperphagic obesity with hyperglycemia and hypertension along with a likely pathogenic variant in the MRAP2 gene [PMID:31700171] and it has been deposited in ClinVar [ClinVar ID: 585350] as Variant of Uncertain Significance. The c.647G>A variant is observed in 33 alleles (~0.006% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8, All ofUs), suggesting it is not a common benign variant in the populations represented in those databases. The c.647G>A variant is located in exon 5 of this 39-exon gene and is predicted to replace an arginine amino acid with histidine at position 216 (p.(Arg216His)). In silico predictions for p.(Arg216His) are inconclusive of the variantβs effect [(CADD v1.6 = 24.8, REVEL = 0.599)]; however, there are no functional studies to support or refute these predictions. Based on available evidence this c.647G>A p.(Arg216His) variant identified in ABCC8 is classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 07, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at