7-147888811-AAAT-A

Variant names:

• chr7-147888811-AAAT-A
• rs10608123
• NM_014141.6:c.2099-14750_2099-14748delAAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014141.6(CNTNAP2):​c.2099-14750_2099-14748delAAT variant causes a intron change involving the alteration of a non-conserved nucleotide. 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
• Publications: 2 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: G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 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.2099-14750_2099-14748delAAT		intron	N/A	NP_054860.1	A0A090N7T7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.2099-14753_2099-14751delAAT		intron	N/A	ENSP00000354778.3	Q9UHC6-1
	CNTNAP2	ENST00000455301.2	TSL:3	n.34-14753_34-14751delAAT		intron	N/A
	CNTNAP2	ENST00000627772.2	TSL:2	n.272-14753_272-14751delAAT		intron	N/A

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

African (AFR) AF: 0.472 AC: 19399 AN: 41100

American (AMR) AF: 0.508 AC: 7581 AN: 14928

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2068 AN: 3436

East Asian (EAS) AF: 0.410 AC: 2071 AN: 5046

South Asian (SAS) AF: 0.456 AC: 2113 AN: 4636

European-Finnish (FIN) AF: 0.438 AC: 4485 AN: 10244

Middle Eastern (MID) AF: 0.523 AC: 139 AN: 266

European-Non Finnish (NFE) AF: 0.497 AC: 33351 AN: 67148

Other (OTH) AF: 0.530 AC: 1090 AN: 2058

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.088
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10608123; hg19: chr7-147585903;