7-147132266-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_014141.6(CNTNAP2):c.1105G>A(p.Val369Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000861 in 1,613,672 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V369L) has been classified as Uncertain significance.
Frequency
Consequence
NM_014141.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.1105G>A | p.Val369Met | missense_variant | 8/24 | ENST00000361727.8 | |
CNTNAP2 | XM_017011950.3 | c.1105G>A | p.Val369Met | missense_variant | 8/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.1105G>A | p.Val369Met | missense_variant | 8/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152054Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251326Hom.: 1 AF XY: 0.000258 AC XY: 35AN XY: 135836
GnomAD4 exome AF: 0.0000896 AC: 131AN: 1461500Hom.: 3 Cov.: 32 AF XY: 0.000132 AC XY: 96AN XY: 727066
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74398
ClinVar
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces valine with methionine at codon 369 of the CNTNAP2 protein (p.Val369Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs368057493, ExAC 0.2%), including at least one homozygous and/or hemizygous individual. 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: 515321). 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: "Benign"; 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at