rs377627481
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014141.6(CNTNAP2):c.1709C>G(p.Ser570Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S570L) has been classified as Uncertain significance.
Frequency
Consequence
NM_014141.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.1709C>G | p.Ser570Trp | missense_variant | 11/24 | ENST00000361727.8 | |
CNTNAP2 | XM_017011950.3 | c.1709C>G | p.Ser570Trp | missense_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.1709C>G | p.Ser570Trp | missense_variant | 11/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727218
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 20, 2020 | 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. 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"). This variant has not been reported in the literature in individuals with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205247). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with tryptophan at codon 570 of the CNTNAP2 protein (p.Ser570Trp). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tryptophan. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 12, 2014 | p.Ser570Trp (TCG>TGG): c.1709 C>G in exon 11 of the CNTNAP2 gene (NM_014141.5). The S570W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S570W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved through mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have notbeen reported. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at