7-146310700-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014141.6(CNTNAP2):​c.97+193727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,898 control chromosomes in the GnomAD database, including 23,850 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 0.51 ( 23850 hom., cov: 31)

Consequence

CNTNAP2
NM_014141.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.254

Publications

2 publications found
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]
CNTNAP2 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AR, AD Classification: DEFINITIVE, NO_KNOWN Submitted by: ClinGen
  • cortical dysplasia-focal epilepsy syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNTNAP2NM_014141.6 linkc.97+193727A>G intron_variant Intron 1 of 23 ENST00000361727.8 NP_054860.1 Q9UHC6-1A0A090N7T7B2RCH4
CNTNAP2XM_017011950.3 linkc.97+193727A>G intron_variant Intron 1 of 13 XP_016867439.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNTNAP2ENST00000361727.8 linkc.97+193727A>G intron_variant Intron 1 of 23 1 NM_014141.6 ENSP00000354778.3 Q9UHC6-1
CNTNAP2ENST00000625365.2 linkc.97+193727A>G intron_variant Intron 2 of 3 5 ENSP00000485955.1 A0A0D9SES4
CNTNAP2ENST00000637150.1 linkn.26+193727A>G intron_variant Intron 1 of 8 5

Frequencies

GnomAD3 genomes
AF:
0.507
AC:
77025
AN:
151778
Hom.:
23782
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.875
Gnomad AMI
AF:
0.422
Gnomad AMR
AF:
0.521
Gnomad ASJ
AF:
0.370
Gnomad EAS
AF:
0.367
Gnomad SAS
AF:
0.296
Gnomad FIN
AF:
0.302
Gnomad MID
AF:
0.548
Gnomad NFE
AF:
0.346
Gnomad OTH
AF:
0.497
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.508
AC:
77147
AN:
151898
Hom.:
23850
Cov.:
31
AF XY:
0.499
AC XY:
37033
AN XY:
74226
show subpopulations
African (AFR)
AF:
0.876
AC:
36330
AN:
41486
American (AMR)
AF:
0.521
AC:
7946
AN:
15242
Ashkenazi Jewish (ASJ)
AF:
0.370
AC:
1283
AN:
3464
East Asian (EAS)
AF:
0.367
AC:
1891
AN:
5156
South Asian (SAS)
AF:
0.294
AC:
1416
AN:
4814
European-Finnish (FIN)
AF:
0.302
AC:
3181
AN:
10546
Middle Eastern (MID)
AF:
0.551
AC:
161
AN:
292
European-Non Finnish (NFE)
AF:
0.346
AC:
23516
AN:
67884
Other (OTH)
AF:
0.494
AC:
1039
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1496
2992
4487
5983
7479
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
620
1240
1860
2480
3100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.412
Hom.:
10441
Bravo
AF:
0.549
Asia WGS
AF:
0.419
AC:
1455
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.25
DANN
Benign
0.30
PhyloP100
-0.25
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs7806058; hg19: chr7-146007792; API