rs535454043
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The ENST00000361727.8(CNTNAP2):c.1566G>A(p.Gln522=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,612,590 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00014 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 4 hom. )
Consequence
CNTNAP2
ENST00000361727.8 synonymous
ENST00000361727.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.03
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 7-147395676-G-A is Benign according to our data. Variant chr7-147395676-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 136813.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1, Likely_benign=2}.
BP7
Synonymous conserved (PhyloP=2.03 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.1566G>A | p.Gln522= | synonymous_variant | 10/24 | ENST00000361727.8 | NP_054860.1 | |
CNTNAP2 | XM_017011950.3 | c.1566G>A | p.Gln522= | synonymous_variant | 10/14 | XP_016867439.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.1566G>A | p.Gln522= | synonymous_variant | 10/24 | 1 | NM_014141.6 | ENSP00000354778 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152028Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000542 AC: 136AN: 251098Hom.: 2 AF XY: 0.000693 AC XY: 94AN XY: 135694
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GnomAD4 exome AF: 0.000217 AC: 317AN: 1460444Hom.: 4 Cov.: 30 AF XY: 0.000310 AC XY: 225AN XY: 726532
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152146Hom.: 1 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74378
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2013 | 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 | Eurofins Ntd Llc (ga) | Sep 28, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 15, 2015 | - - |
Cortical dysplasia-focal epilepsy syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 17, 2017 | This alteration is classified as likely 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at