7-147494245-T-C

Variant names:

• chr7-147494245-T-C
• rs1015932
• NM_014141.6:c.1777+8204T>C

Variant summary

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

The NM_014141.6(CNTNAP2):​c.1777+8204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,850 control chromosomes in the GnomAD database, including 36,916 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 0.70 (36916 hom., cov: 31)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014141.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	NM_014141.6	MANE Select	c.1777+8204T>C		intron	N/A	NP_054860.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.1777+8204T>C		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000636870.1	TSL:5	n.1639+8204T>C		intron	N/A
	CNTNAP2	ENST00000637694.1	TSL:5	n.1681-2376T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105568 AN: 151732 Hom.: 36904 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.696 AC: 105623 AN: 151850 Hom.: 36916 Cov.: 31 AF XY: 0.693 AC XY: 51408 AN XY: 74202

African (AFR) AF: 0.738 AC: 30549 AN: 41400

American (AMR) AF: 0.642 AC: 9773 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2488 AN: 3470

East Asian (EAS) AF: 0.581 AC: 2990 AN: 5148

South Asian (SAS) AF: 0.555 AC: 2669 AN: 4808

European-Finnish (FIN) AF: 0.714 AC: 7521 AN: 10534

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47386 AN: 67946

Other (OTH) AF: 0.697 AC: 1469 AN: 2108

Alfa AF: 0.700 Hom.: 50707

Bravo AF: 0.693

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.58
PhyloP100		0.70
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: rs1015932; hg19: chr7-147191337;