rs760047247
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014141.6(CNTNAP2):c.3833C>T(p.Thr1278Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_014141.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.3833C>T | p.Thr1278Ile | missense_variant | Exon 24 of 24 | ENST00000361727.8 | NP_054860.1 | |
LOC105375554 | XR_928094.2 | n.210-20761G>A | intron_variant | Intron 1 of 3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251236Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135794
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461794Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727200
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74378
ClinVar
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1278 of the CNTNAP2 protein (p.Thr1278Ile). This variant is present in population databases (rs760047247, gnomAD 0.005%). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 18179895). ClinVar contains an entry for this variant (Variation ID: 585729). 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"). Experimental studies have shown that this missense change affects CNTNAP2 function (PMID: 22872700). 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 Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at