7-147903704-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014141.6(CNTNAP2):c.2238C>A(p.Asp746Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,688 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. D746N) 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.2238C>A | p.Asp746Glu | missense_variant | 14/24 | ENST00000361727.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.2238C>A | p.Asp746Glu | missense_variant | 14/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249328Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134766
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461498Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727004
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74350
ClinVar
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2021 | This sequence change replaces aspartic acid with glutamic acid at codon 746 of the CNTNAP2 protein (p.Asp746Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs375648820, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at