rs10282158

Variant names:

• chr7-147040975-T-A
• rs10282158
• NM_014141.6:c.403-2932T>A

Variant summary

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

The NM_014141.6(CNTNAP2):​c.403-2932T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,104 control chromosomes in the GnomAD database, including 3,308 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 0.16 (3308 hom., cov: 31)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.403-2932T>A		intron_variant	Intron 3 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.403-2932T>A		intron_variant	Intron 3 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.403-2932T>A		intron_variant	Intron 3 of 23	1	NM_014141.6	ENSP00000354778.3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24317 AN: 151988 Hom.: 3295 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.160 AC: 24379 AN: 152104 Hom.: 3308 Cov.: 31 AF XY: 0.158 AC XY: 11776 AN XY: 74370

African (AFR) AF: 0.360 AC: 14939 AN: 41442

American (AMR) AF: 0.175 AC: 2670 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 295 AN: 3460

East Asian (EAS) AF: 0.232 AC: 1197 AN: 5168

South Asian (SAS) AF: 0.139 AC: 672 AN: 4826

European-Finnish (FIN) AF: 0.0316 AC: 336 AN: 10618

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0570 AC: 3876 AN: 67986

Other (OTH) AF: 0.148 AC: 312 AN: 2110

Alfa AF: 0.123 Hom.: 248

Bravo AF: 0.182

Asia WGS AF: 0.178 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.57
PhyloP100		-0.81
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: rs10282158; hg19: chr7-146738067; COSMIC: COSV62214229; COSMIC: COSV62214229;