rs72268642
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The ENST00000361727.8(CNTNAP2):c.3716-7_3716-6insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,578,214 control chromosomes in the GnomAD database, including 252,035 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.57 ( 25625 hom., cov: 33)
Exomes 𝑓: 0.56 ( 226410 hom. )
Consequence
CNTNAP2
ENST00000361727.8 splice_region, splice_polypyrimidine_tract, intron
ENST00000361727.8 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.173
Genes affected
CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 7-148409383-C-CTT is Benign according to our data. Variant chr7-148409383-C-CTT is described in ClinVar as [Benign]. Clinvar id is 516869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.3716-7_3716-6insTT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000361727.8 | NP_054860.1 | |||
LOC105375554 | XR_928094.2 | n.210-14692_210-14691insAA | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.3716-7_3716-6insTT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014141.6 | ENSP00000354778 | P1 |
Frequencies
GnomAD3 genomes AF: 0.574 AC: 86906AN: 151482Hom.: 25607 Cov.: 33
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GnomAD3 exomes AF: 0.293 AC: 59553AN: 203228Hom.: 20501 AF XY: 0.303 AC XY: 33053AN XY: 108920
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GnomAD4 exome AF: 0.556 AC: 793079AN: 1426614Hom.: 226410 Cov.: 30 AF XY: 0.558 AC XY: 396955AN XY: 711266
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GnomAD4 genome AF: 0.574 AC: 86958AN: 151600Hom.: 25625 Cov.: 33 AF XY: 0.570 AC XY: 42224AN XY: 74094
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cortical dysplasia-focal epilepsy syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 19, 2019 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at