ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.2497del (p.Trp833fs)

gnomAD frequency: 0.00001  dbSNP: rs1391540245
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644701 SCV000766404 pathogenic Cortical dysplasia-focal epilepsy syndrome 2024-10-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp833Glyfs*18) in the CNTNAP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNTNAP2 are known to be pathogenic (PMID: 19896112, 21827697, 25045150, 26843181, 27439707). This variant is not present in population databases (gnomAD no frequency). 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: 536312). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001541691 SCV001759718 pathogenic not provided 2024-03-05 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34926809, 31440721)
New York Genome Center RCV000644701 SCV002548923 likely pathogenic Cortical dysplasia-focal epilepsy syndrome 2021-05-27 criteria provided, single submitter clinical testing The homozygous c.2497del (p.Trp833GlyfsTer18) variant identified in the CNTNAP2 gene is the deletion of a single nucleotide resulting in the frameshift of the protein at amino acid 833/1332 (exon 16/24). This variant is found with low frequency in gnomAD(v3.1.1) (2 heterozygotes, 0 homozygotes; allelefrequency:1.31e-5) suggesting it is not a common benign variant in the populations represented in that database. The c.2497del (p.Trp833GlyfsTer18) variant isreported in ClinVar as Pathogenic (VarID:536312) and to our current knowledge has not been reported in affected individuals in the literature, although nonsense and frameshift variants downstream of this one have been reported in affected individuals [PMID:27439707]. Given its deleterious nature and absence in population databases, the homozygous c.2497del (p.Trp833GlyfsTer18) variant identified in the CNTNAP2 gene is reported as Likely Pathogenic.
Ambry Genetics RCV002424472 SCV002741071 pathogenic Inborn genetic diseases 2022-08-17 criteria provided, single submitter clinical testing The c.2497delT (p.W833Gfs*18) alteration, located in exon 16 (coding exon 16) of the CNTNAP2 gene, consists of a deletion of one nucleotide at position 2497, causing a translational frameshift with a predicted alternate stop codon after 18 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005046829 SCV005667276 pathogenic Autism, susceptibility to, 15; Cortical dysplasia-focal epilepsy syndrome 2024-02-15 criteria provided, single submitter clinical testing

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