1-235759143-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000081.4(LYST):c.6710A>G(p.Gln2237Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q2237P) has been classified as Likely benign.
Frequency
Consequence
NM_000081.4 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 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250670Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135438
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461840Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727218
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Chédiak-Higashi syndrome Uncertain:1
This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 2237 of the LYST protein (p.Gln2237Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LYST-related conditions. ClinVar contains an entry for this variant (Variation ID: 854925). 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 LYST protein function. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at