rs10608123

chr7-147888811-AAAT-Achr7-147888811-AAAT-AAATAAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014141.6(CNTNAP2):c.2099-14750_2099-14748del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 149,760 control chromosomes in the GnomAD database, including 17,666 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17666 hom., cov: 0)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP2	NM_014141.6	c.2099-14750_2099-14748del		intron_variant		ENST00000361727.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.2099-14750_2099-14748del		intron_variant		1	NM_014141.6	P1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 72556 AN: 149640 Hom.: 17650 Cov.: 0

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.485 AC: 72610 AN: 149760 Hom.: 17666 Cov.: 0 AF XY: 0.481 AC XY: 35115 AN XY: 73060

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.530

Alfa AF: 0.490 Hom.: 2259

Bravo AF: 0.495

Asia WGS AF: 0.471 AC: 1637 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs10608123; hg19: chr7-147585903;