rs150607716
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_014141.6(CNTNAP2):āc.387A>Gā(p.Gln129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,614,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: š 0.00034 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
CNTNAP2
NM_014141.6 synonymous
NM_014141.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.185
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 7-146839889-A-G is Benign according to our data. Variant chr7-146839889-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 288881.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-0.185 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNTNAP2 | NM_014141.6 | c.387A>G | p.Gln129= | synonymous_variant | 3/24 | ENST00000361727.8 | |
CNTNAP2 | XM_017011950.3 | c.387A>G | p.Gln129= | synonymous_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNTNAP2 | ENST00000361727.8 | c.387A>G | p.Gln129= | synonymous_variant | 3/24 | 1 | NM_014141.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152246Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251310Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135820
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727220
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GnomAD4 genome ? AF: 0.000341 AC: 52AN: 152364Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29AN XY: 74518
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 19, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 23, 2018 | - - |
Cortical dysplasia-focal epilepsy syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
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