7-148229753-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014141.6(CNTNAP2):c.3355C>T(p.Arg1119Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000545 in 1,613,920 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1119H) has been classified as Uncertain significance.
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.3355C>T | p.Arg1119Cys | missense_variant | 20/24 | ENST00000361727.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.3355C>T | p.Arg1119Cys | missense_variant | 20/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251340Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135854
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1461844Hom.: 0 Cov.: 34 AF XY: 0.0000523 AC XY: 38AN XY: 727228
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74270
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 01, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); 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: 27535533, 22872700, 18179895) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 11, 2015 | - - |
Cortical dysplasia-focal epilepsy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1119 of the CNTNAP2 protein (p.Arg1119Cys). This variant is present in population databases (rs367664952, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of CNTNAP2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 195509). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The c.3355C>T (p.R1119C) alteration is located in exon 20 (coding exon 20) of the CNTNAP2 gene. This alteration results from a C to T substitution at nucleotide position 3355, causing the arginine (R) at amino acid position 1119 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autism, susceptibility to, 15;C2750246:Cortical dysplasia-focal epilepsy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 28, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at