7-146425696-T-C

Variant names:

• chr7-146425696-T-C
• rs1718101
• NM_014141.6:c.97+308723T>C

Variant summary

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

The NM_014141.6(CNTNAP2):​c.97+308723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 152,218 control chromosomes in the GnomAD database, including 71,257 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 0.97 (71257 hom., cov: 30)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 10 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 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.97+308723T>C		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.97+308723T>C		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000625365.2	TSL:5	c.97+308723T>C		intron	N/A	ENSP00000485955.1
	CNTNAP2	ENST00000637150.1	TSL:5	n.26+308723T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147108 AN: 152100 Hom.: 71195 Cov.: 30

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.967

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

GnomAD4 genome AF: 0.967 AC: 147230 AN: 152218 Hom.: 71257 Cov.: 30 AF XY: 0.969 AC XY: 72142 AN XY: 74414

African (AFR) AF: 0.991 AC: 41166 AN: 41532

American (AMR) AF: 0.966 AC: 14786 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3355 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5152 AN: 5152

South Asian (SAS) AF: 0.993 AC: 4790 AN: 4824

European-Finnish (FIN) AF: 0.978 AC: 10363 AN: 10598

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64423 AN: 68022

Other (OTH) AF: 0.968 AC: 2044 AN: 2112

Alfa AF: 0.955 Hom.: 30236

Bravo AF: 0.967

Asia WGS AF: 0.993 AC: 3454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.75
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: rs1718101; hg19: chr7-146122788;