chr7-44147729-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_000162.5(GCK):c.784G>A(p.Asp262Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,440 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain risk allele (★★).
Frequency
Consequence
NM_000162.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152258Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251030Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135786
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461182Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726930
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74396
ClinVar
Submissions by phenotype
not specified Uncertain:1
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not provided Uncertain:1
This variant has not been reported in the literature in individuals affected with GCK-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GCK protein function. ClinVar contains an entry for this variant (Variation ID: 211075). This variant is present in population databases (rs779460424, gnomAD 0.004%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 262 of the GCK protein (p.Asp262Asn). -
Type 2 diabetes mellitus;C0342277:Maturity-onset diabetes of the young type 2;C1865290:Hyperinsulinism due to glucokinase deficiency;C5393570:Permanent neonatal diabetes mellitus 1 Uncertain:1
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Maturity onset diabetes mellitus in young Other:1
Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs779460424 in MODY, yet. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at