7-147935043-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014141.6(CNTNAP2):​c.2255+31322G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,574 control chromosomes in the GnomAD database, including 40,344 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 40344 hom., cov: 32)

Consequence

CNTNAP2
NM_014141.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170
Variant links:
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNTNAP2NM_014141.6 linkc.2255+31322G>C intron_variant Intron 14 of 23 ENST00000361727.8 NP_054860.1 Q9UHC6-1A0A090N7T7B2RCH4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNTNAP2ENST00000361727.8 linkc.2255+31322G>C intron_variant Intron 14 of 23 1 NM_014141.6 ENSP00000354778.3 Q9UHC6-1

Frequencies

GnomAD3 genomes
AF:
0.695
AC:
105289
AN:
151478
Hom.:
40327
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.339
Gnomad AMI
AF:
0.854
Gnomad AMR
AF:
0.798
Gnomad ASJ
AF:
0.887
Gnomad EAS
AF:
0.729
Gnomad SAS
AF:
0.768
Gnomad FIN
AF:
0.780
Gnomad MID
AF:
0.838
Gnomad NFE
AF:
0.852
Gnomad OTH
AF:
0.743
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.695
AC:
105334
AN:
151574
Hom.:
40344
Cov.:
32
AF XY:
0.695
AC XY:
51491
AN XY:
74080
show subpopulations
Gnomad4 AFR
AF:
0.339
Gnomad4 AMR
AF:
0.798
Gnomad4 ASJ
AF:
0.887
Gnomad4 EAS
AF:
0.729
Gnomad4 SAS
AF:
0.769
Gnomad4 FIN
AF:
0.780
Gnomad4 NFE
AF:
0.852
Gnomad4 OTH
AF:
0.744
Alfa
AF:
0.757
Hom.:
5772
Bravo
AF:
0.679
Asia WGS
AF:
0.718
AC:
2492
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.4
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2710093; hg19: chr7-147632135; API