7-147067905-G-A

Variant names:

• chr7-147067905-G-A
• rs2159473
• NM_014141.6:c.550+23851G>A

Variant summary

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

The NM_014141.6(CNTNAP2):​c.550+23851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,024 control chromosomes in the GnomAD database, including 28,487 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 0.60 (28487 hom., cov: 33)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.853
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 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.550+23851G>A		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.550+23851G>A		intron	N/A	ENSP00000354778.3	Q9UHC6-1
	CNTNAP2	ENST00000636561.1	TSL:5	n.453+23851G>A		intron	N/A
	CNTNAP2	ENST00000636870.1	TSL:5	n.412+23851G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90689 AN: 151902 Hom.: 28489 Cov.: 33

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.597 AC: 90708 AN: 152024 Hom.: 28487 Cov.: 33 AF XY: 0.602 AC XY: 44728 AN XY: 74324

African (AFR) AF: 0.381 AC: 15767 AN: 41412

American (AMR) AF: 0.634 AC: 9682 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2136 AN: 3472

East Asian (EAS) AF: 0.732 AC: 3787 AN: 5176

South Asian (SAS) AF: 0.608 AC: 2933 AN: 4824

European-Finnish (FIN) AF: 0.763 AC: 8064 AN: 10570

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46377 AN: 67982

Other (OTH) AF: 0.586 AC: 1241 AN: 2116

Alfa AF: 0.624 Hom.: 4538

Bravo AF: 0.579

Asia WGS AF: 0.615 AC: 2139 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	2.2
DANN	Benign	0.62
PhyloP100		0.85
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: rs2159473; hg19: chr7-146764997;