rs201649365
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_005076.5(CNTN2):c.2686A>T(p.Thr896Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T896T) has been classified as Uncertain significance.
Frequency
Consequence
NM_005076.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTN2 | NM_005076.5 | c.2686A>T | p.Thr896Ser | missense_variant | 20/23 | ENST00000331830.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTN2 | ENST00000331830.7 | c.2686A>T | p.Thr896Ser | missense_variant | 20/23 | 1 | NM_005076.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000598 AC: 15AN: 250690Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135496
GnomAD4 exome AF: 0.000136 AC: 199AN: 1461380Hom.: 0 Cov.: 34 AF XY: 0.000133 AC XY: 97AN XY: 727030
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74456
ClinVar
Submissions by phenotype
Epilepsy, familial adult myoclonic, 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 896 of the CNTN2 protein (p.Thr896Ser). This variant is present in population databases (rs201649365, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CNTN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 572166). 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 CNTN2 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