rs1860681

Variant names:

• chr7-146359328-C-T
• rs1860681
• NM_014141.6:c.97+242355C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014141.6(CNTNAP2):​c.97+242355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,204 control chromosomes in the GnomAD database, including 4,330 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 0.15 (4330 hom., cov: 33)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 1 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.97+242355C>T		intron_variant	Intron 1 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.97+242355C>T		intron_variant	Intron 1 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.97+242355C>T		intron_variant	Intron 1 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000625365.2	c.97+242355C>T		intron_variant	Intron 2 of 3	5		ENSP00000485955.1
CNTNAP2	ENST00000637150.1	n.26+242355C>T		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22551 AN: 152086 Hom.: 4290 Cov.: 33

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0287

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.135

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.149 AC: 22637 AN: 152204 Hom.: 4330 Cov.: 33 AF XY: 0.147 AC XY: 10931 AN XY: 74418

African (AFR) AF: 0.444 AC: 18426 AN: 41506

American (AMR) AF: 0.0747 AC: 1142 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3472

East Asian (EAS) AF: 0.0287 AC: 149 AN: 5184

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4830

European-Finnish (FIN) AF: 0.0637 AC: 675 AN: 10598

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0211 AC: 1432 AN: 68014

Other (OTH) AF: 0.134 AC: 282 AN: 2112

Alfa AF: 0.0667 Hom.: 1826

Bravo AF: 0.164

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.46
PhyloP100		-1.4
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

Other links and lift over

dbSNP: rs1860681; hg19: chr7-146056420;