rs201326295
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_014141.6(CNTNAP2):āc.515T>Cā(p.Ile172Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,614,182 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I172I) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.515T>C | p.Ile172Thr | missense_variant | 4/24 | ENST00000361727.8 | |
CNTNAP2 | XM_017011950.3 | c.515T>C | p.Ile172Thr | missense_variant | 4/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.515T>C | p.Ile172Thr | missense_variant | 4/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000445 AC: 112AN: 251442Hom.: 1 AF XY: 0.000486 AC XY: 66AN XY: 135896
GnomAD4 exome AF: 0.000116 AC: 169AN: 1461840Hom.: 2 Cov.: 31 AF XY: 0.000125 AC XY: 91AN XY: 727224
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74502
ClinVar
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 01, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 02, 2017 | p.I172T (ATT>ACT): c.515T>C in CNTNAP2 gene (NM_014141.5). The Ile172Thr missense change 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 amino acid substitution is non-conservative, as a non-polar Isoleucine residue is replaced by a polar Threonine residue. It alters a position in the F5/8 type C domain of the protein that is conserved through mammals, but Threonine is observed at this position in more distant species in evolution. Missense mutations have not been reported in this region of the protein, and multiple in silico algorithms predict Ile172Thr is likely benign. The identification of Ile172Thr an unaffected parent provided additional evidence to suggest that this variant is benign; however, the possibility that it is a disease-causing mutation cannot be excluded, as heterozygous mutations in CNTNAP2 have been identified in unaffected individuals, demonstrating incomplete penetrance (Elia et al., 2010; Gregor et al., 2011; Bakkaloglu et al., 2008; O'Roak et al., 2011; Mefford et al., 2010; Poot et al., 2010). The variant is found in INFANT-EPI,EPILEPSY panel(s). - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 07, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at