chr6-10528925-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_145649.5(GCNT2):c.14G>A(p.Trp5*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_145649.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000316 AC: 48AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000298 AC: 75AN: 251356Hom.: 0 AF XY: 0.000353 AC XY: 48AN XY: 135892
GnomAD4 exome AF: 0.000144 AC: 211AN: 1460640Hom.: 0 Cov.: 31 AF XY: 0.000186 AC XY: 135AN XY: 726740
GnomAD4 genome AF: 0.000315 AC: 48AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33AN XY: 74434
ClinVar
Submissions by phenotype
Cataract 13 with adult I phenotype Pathogenic:1
Evidence categories PVS1, PM2 and PM4 in ACMG guidelines. This stop-gained variant in gene GCNT2 leads to a premature termination codon NP_001361676.1:p.Trp5Ter and disrupts the whole protein. -
GCNT2-related disorder Uncertain:1
The GCNT2 c.14G>A variant is predicted to result in premature protein termination (p.Trp5*). In the tissue specific transcript found within the lens of the eye (NM_001491.2), this variant is found within a non-coding region (c.-27499G>A). To our knowledge, this variant has not been documented in the literature. This variant is reported in 0.17% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at