rs7803877

Variant names:

• chr7-147408816-A-G
• rs7803877
• NM_014141.6:c.1670+13036A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-147408816-A-G
• chr7-147408816-A-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.1670+13036A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,030 control chromosomes in the GnomAD database, including 19,640 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 0.47 (19640 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 3 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 = 0.764 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	NM_014141.6	MANE Select	c.1670+13036A>G		intron	N/A	NP_054860.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.1670+13036A>G		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000636870.1	TSL:5	n.1532+13036A>G		intron	N/A
	CNTNAP2	ENST00000637694.1	TSL:5	n.1573+13036A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71486 AN: 151912 Hom.: 19601 Cov.: 32

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.471 AC: 71574 AN: 152030 Hom.: 19640 Cov.: 32 AF XY: 0.466 AC XY: 34628 AN XY: 74324

African (AFR) AF: 0.771 AC: 31954 AN: 41466

American (AMR) AF: 0.411 AC: 6279 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1303 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2126 AN: 5144

South Asian (SAS) AF: 0.440 AC: 2122 AN: 4818

European-Finnish (FIN) AF: 0.293 AC: 3102 AN: 10586

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23348 AN: 67960

Other (OTH) AF: 0.419 AC: 884 AN: 2110

Alfa AF: 0.422 Hom.: 2677

Bravo AF: 0.492

Asia WGS AF: 0.415 AC: 1446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.32
PhyloP100		-0.28
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: rs7803877; hg19: chr7-147105908;