7-147932395-A-G

Variant names:

• chr7-147932395-A-G
• rs2710091
• NM_014141.6:c.2255+28674A>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.2255+28674A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,094 control chromosomes in the GnomAD database, including 41,212 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 0.70 (41212 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 6 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 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.2255+28674A>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.2255+28674A>G		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000455301.2	TSL:3	n.190+28674A>G		intron	N/A
	CNTNAP2	ENST00000627772.2	TSL:2	n.428+28674A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107122 AN: 151976 Hom.: 41195 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.705 AC: 107175 AN: 152094 Hom.: 41212 Cov.: 32 AF XY: 0.706 AC XY: 52504 AN XY: 74340

African (AFR) AF: 0.364 AC: 15095 AN: 41434

American (AMR) AF: 0.800 AC: 12237 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3076 AN: 3466

East Asian (EAS) AF: 0.743 AC: 3839 AN: 5170

South Asian (SAS) AF: 0.770 AC: 3709 AN: 4816

European-Finnish (FIN) AF: 0.814 AC: 8619 AN: 10582

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58002 AN: 68014

Other (OTH) AF: 0.747 AC: 1574 AN: 2108

Alfa AF: 0.810 Hom.: 197912

Bravo AF: 0.689

Asia WGS AF: 0.729 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.38
PhyloP100		-0.61
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: rs2710091; hg19: chr7-147629487;