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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.173
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 -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
CNTNAP2NM_014141.6 linkuse as main transcriptc.3716-7_3716-6insTT splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000361727.8 NP_054860.1
LOC105375554XR_928094.2 linkuse as main transcriptn.210-14692_210-14691insAA intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CNTNAP2ENST00000361727.8 linkuse as main transcriptc.3716-7_3716-6insTT splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_014141.6 ENSP00000354778 P1Q9UHC6-1

Frequencies

GnomAD3 genomes
AF:
0.574
AC:
86906
AN:
151482
Hom.:
25607
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.659
Gnomad AMI
AF:
0.467
Gnomad AMR
AF:
0.393
Gnomad ASJ
AF:
0.467
Gnomad EAS
AF:
0.374
Gnomad SAS
AF:
0.618
Gnomad FIN
AF:
0.654
Gnomad MID
AF:
0.414
Gnomad NFE
AF:
0.571
Gnomad OTH
AF:
0.536
GnomAD3 exomes
AF:
0.293
AC:
59553
AN:
203228
Hom.:
20501
AF XY:
0.303
AC XY:
33053
AN XY:
108920
show subpopulations
Gnomad AFR exome
AF:
0.372
Gnomad AMR exome
AF:
0.0826
Gnomad ASJ exome
AF:
0.273
Gnomad EAS exome
AF:
0.134
Gnomad SAS exome
AF:
0.357
Gnomad FIN exome
AF:
0.422
Gnomad NFE exome
AF:
0.340
Gnomad OTH exome
AF:
0.273
GnomAD4 exome
AF:
0.556
AC:
793079
AN:
1426614
Hom.:
226410
Cov.:
30
AF XY:
0.558
AC XY:
396955
AN XY:
711266
show subpopulations
Gnomad4 AFR exome
AF:
0.659
Gnomad4 AMR exome
AF:
0.310
Gnomad4 ASJ exome
AF:
0.464
Gnomad4 EAS exome
AF:
0.354
Gnomad4 SAS exome
AF:
0.615
Gnomad4 FIN exome
AF:
0.652
Gnomad4 NFE exome
AF:
0.564
Gnomad4 OTH exome
AF:
0.547
GnomAD4 genome
AF:
0.574
AC:
86958
AN:
151600
Hom.:
25625
Cov.:
33
AF XY:
0.570
AC XY:
42224
AN XY:
74094
show subpopulations
Gnomad4 AFR
AF:
0.658
Gnomad4 AMR
AF:
0.392
Gnomad4 ASJ
AF:
0.467
Gnomad4 EAS
AF:
0.373
Gnomad4 SAS
AF:
0.618
Gnomad4 FIN
AF:
0.654
Gnomad4 NFE
AF:
0.571
Gnomad4 OTH
AF:
0.537
Alfa
AF:
0.457
Hom.:
2530
Asia WGS
AF:
0.515
AC:
1794
AN:
3478

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 19, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs72268642; hg19: chr7-148106475; API