Variant rs72268642 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_014141.6(CNTNAP2):c.3716-7_3716-6insTT variant causes a splice region, 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
NM_014141.6 splice_region, 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]

CNTNAP2 links:

CNTNAP2 (HGNC:):

CNTNAP2 links:

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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
CNTNAP2	NM_014141.6 linkuse as main transcript	c.3716-7_3716-6insTT		splice_region_variant, intron_variant		ENST00000361727.8	NP_054860.1	Q9UHC6-1A0A090N7T7B2RCH4
LOC105375554	XR_928094.2 linkuse as main transcript	n.210-14692_210-14691insAA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8 linkuse as main transcript	c.3716-7_3716-6insTT		splice_region_variant, intron_variant		1	NM_014141.6	ENSP00000354778.3		Q9UHC6-1

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

86906

AN:

151482

Hom.:

25607

Cov.:

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.:

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.:

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 submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over