chr7-147977962-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014141.6(CNTNAP2):c.2356G>T(p.Val786Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,614,102 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V786I) has been classified as Likely benign.
Frequency
Consequence
NM_014141.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.2356G>T | p.Val786Leu | missense_variant | 15/24 | ENST00000361727.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.2356G>T | p.Val786Leu | missense_variant | 15/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000999 AC: 152AN: 152144Hom.: 3 Cov.: 31
GnomAD3 exomes AF: 0.00372 AC: 936AN: 251428Hom.: 18 AF XY: 0.00501 AC XY: 681AN XY: 135896
GnomAD4 exome AF: 0.00227 AC: 3320AN: 1461840Hom.: 77 Cov.: 32 AF XY: 0.00306 AC XY: 2222AN XY: 727224
GnomAD4 genome ? AF: 0.000985 AC: 150AN: 152262Hom.: 3 Cov.: 31 AF XY: 0.00140 AC XY: 104AN XY: 74446
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 24, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 25, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 25, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 23, 2017 | - - |
Cortical dysplasia-focal epilepsy syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2017 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Pitt-Hopkins-like syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | CNTNAP2: BS1, BS2 - |
CNTNAP2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 23, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at