rs779208613
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014141.6(CNTNAP2):āc.338A>Gā(p.Tyr113Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_014141.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.338A>G | p.Tyr113Cys | missense_variant | 3/24 | ENST00000361727.8 | |
CNTNAP2 | XM_017011950.3 | c.338A>G | p.Tyr113Cys | missense_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.338A>G | p.Tyr113Cys | missense_variant | 3/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251444Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135898
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727234
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74332
ClinVar
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 113 of the CNTNAP2 protein (p.Tyr113Cys). This variant is present in population databases (rs779208613, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 411995). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | Revvity Omics, Revvity | Mar 23, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2020 | 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; This variant is associated with the following publications: (PMID: 32381728) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at