rs11975946

Variant names:

• chr7-147614261-A-G
• rs11975946
• NM_014141.6:c.1898-24845A>G

Variant summary

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

The NM_014141.6(CNTNAP2):​c.1898-24845A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,862 control chromosomes in the GnomAD database, including 12,231 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 0.40 (12231 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.435 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.1898-24845A>G		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.1898-24845A>G		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000636870.1	TSL:5	n.1760-24845A>G		intron	N/A
	CNTNAP2	ENST00000637825.1	TSL:5	n.1381-24845A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60816 AN: 151744 Hom.: 12226 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.401 AC: 60847 AN: 151862 Hom.: 12231 Cov.: 32 AF XY: 0.400 AC XY: 29682 AN XY: 74228

African (AFR) AF: 0.346 AC: 14330 AN: 41440

American (AMR) AF: 0.444 AC: 6765 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1754 AN: 5146

South Asian (SAS) AF: 0.393 AC: 1892 AN: 4810

European-Finnish (FIN) AF: 0.417 AC: 4390 AN: 10520

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28905 AN: 67914

Other (OTH) AF: 0.386 AC: 812 AN: 2104

Alfa AF: 0.414 Hom.: 18947

Bravo AF: 0.398

Asia WGS AF: 0.386 AC: 1339 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.80
PhyloP100		0.095
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: rs11975946; hg19: chr7-147311353;