rs11771941

Variant names:

• chr7-147982443-G-A
• rs11771941
• NM_014141.6:c.2383+4454G>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.2383+4454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,050 control chromosomes in the GnomAD database, including 12,200 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 0.37 (12200 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.2383+4454G>A		intron_variant	Intron 15 of 23	ENST00000361727.8	NP_054860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.2383+4454G>A		intron_variant	Intron 15 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000627772.2	n.556+4454G>A		intron_variant	Intron 4 of 12	2
CNTNAP2	ENST00000636870.1	n.2245+4454G>A		intron_variant	Intron 13 of 21	5
CNTNAP2	ENST00000637825.1	n.1866+4454G>A		intron_variant	Intron 12 of 13	5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55853 AN: 151932 Hom.: 12206 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.367 AC: 55847 AN: 152050 Hom.: 12200 Cov.: 32 AF XY: 0.364 AC XY: 27058 AN XY: 74318

African (AFR) AF: 0.146 AC: 6043 AN: 41496

American (AMR) AF: 0.338 AC: 5160 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3470

East Asian (EAS) AF: 0.162 AC: 835 AN: 5160

South Asian (SAS) AF: 0.506 AC: 2438 AN: 4814

European-Finnish (FIN) AF: 0.373 AC: 3944 AN: 10574

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33626 AN: 67958

Other (OTH) AF: 0.433 AC: 913 AN: 2108

Alfa AF: 0.464 Hom.: 32255

Bravo AF: 0.351

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.78
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: rs11771941; hg19: chr7-147679535;