7-147935043-G-C

Variant names:

• chr7-147935043-G-C
• rs2710093
• NM_014141.6:c.2255+31322G>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.2255+31322G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,574 control chromosomes in the GnomAD database, including 40,344 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 0.69 (40344 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.2255+31322G>C		intron_variant	Intron 14 of 23	ENST00000361727.8	NP_054860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.2255+31322G>C		intron_variant	Intron 14 of 23	1	NM_014141.6	ENSP00000354778.3

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105289 AN: 151478 Hom.: 40327 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.695 AC: 105334 AN: 151574 Hom.: 40344 Cov.: 32 AF XY: 0.695 AC XY: 51491 AN XY: 74080

African (AFR) AF: 0.339 AC: 13933 AN: 41132

American (AMR) AF: 0.798 AC: 12171 AN: 15252

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

East Asian (EAS) AF: 0.729 AC: 3773 AN: 5176

South Asian (SAS) AF: 0.769 AC: 3698 AN: 4810

European-Finnish (FIN) AF: 0.780 AC: 8154 AN: 10450

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.852 AC: 57933 AN: 67968

Other (OTH) AF: 0.744 AC: 1570 AN: 2110

Alfa AF: 0.757 Hom.: 5772

Bravo AF: 0.679

Asia WGS AF: 0.718 AC: 2492 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-0.017
Mutation Taster		=99/1	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: rs2710093; hg19: chr7-147632135;