7-147934809-A-G

Variant names:

• chr7-147934809-A-G
• rs2253031
• NM_014141.6:c.2255+31088A>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+31088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,020 control chromosomes in the GnomAD database, including 40,772 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 (40772 hom., cov: 31)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.846 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.2255+31088A>G		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.2255+31088A>G		intron	N/A	ENSP00000354778.3	Q9UHC6-1
	CNTNAP2	ENST00000455301.2	TSL:3	n.190+31088A>G		intron	N/A
	CNTNAP2	ENST00000627772.2	TSL:2	n.428+31088A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106562 AN: 151902 Hom.: 40754 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.701 AC: 106616 AN: 152020 Hom.: 40772 Cov.: 31 AF XY: 0.701 AC XY: 52084 AN XY: 74300

African (AFR) AF: 0.364 AC: 15110 AN: 41454

American (AMR) AF: 0.800 AC: 12225 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3080 AN: 3472

East Asian (EAS) AF: 0.729 AC: 3755 AN: 5150

South Asian (SAS) AF: 0.769 AC: 3702 AN: 4814

European-Finnish (FIN) AF: 0.778 AC: 8205 AN: 10546

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

European-Non Finnish (NFE) AF: 0.852 AC: 57937 AN: 67982

Other (OTH) AF: 0.747 AC: 1578 AN: 2112

Alfa AF: 0.608 Hom.: 2592

Bravo AF: 0.689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.62
PhyloP100		-0.26
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: rs2253031; hg19: chr7-147631901;