chr16-88709994-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001012759.3(CTU2):c.200G>A(p.Arg67Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000734 in 1,613,924 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. R67W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001012759.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTU2 | NM_001012759.3 | c.200G>A | p.Arg67Gln | missense_variant | 3/15 | ENST00000453996.7 | |
CTU2 | NM_001318507.2 | c.200G>A | p.Arg67Gln | missense_variant | 3/15 | ||
CTU2 | NM_001012762.3 | c.200G>A | p.Arg67Gln | missense_variant | 3/14 | ||
CTU2 | NM_001318513.2 | c.-39-229G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTU2 | ENST00000453996.7 | c.200G>A | p.Arg67Gln | missense_variant | 3/15 | 1 | NM_001012759.3 | P2 | |
ENST00000616106.1 | n.444C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.000670 AC: 102AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000665 AC: 167AN: 251316Hom.: 1 AF XY: 0.000662 AC XY: 90AN XY: 135882
GnomAD4 exome AF: 0.000740 AC: 1082AN: 1461612Hom.: 3 Cov.: 32 AF XY: 0.000755 AC XY: 549AN XY: 727098
GnomAD4 genome ? AF: 0.000670 AC: 102AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 67 of the CTU2 protein (p.Arg67Gln). This variant is present in population databases (rs149997219, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with CTU2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1448262). 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 expected to disrupt CTU2 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 27, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2022 | The c.200G>A (p.R67Q) alteration is located in exon 3 (coding exon 3) of the CTU2 gene. This alteration results from a G to A substitution at nucleotide position 200, causing the arginine (R) at amino acid position 67 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at