rs802571

Variant names:

• chr7-146265094-A-G
• rs802571
• NM_014141.6:c.97+148121A>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.97+148121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,164 control chromosomes in the GnomAD database, including 9,631 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 0.21 (9631 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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.97+148121A>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.97+148121A>G		intron	N/A	ENSP00000354778.3	Q9UHC6-1
	CNTNAP2	ENST00000625365.2	TSL:5	c.97+148121A>G		intron	N/A	ENSP00000485955.1	A0A0D9SES4
	CNTNAP2	ENST00000637150.1	TSL:5	n.26+148121A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32591 AN: 152046 Hom.: 9577 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.215 AC: 32695 AN: 152164 Hom.: 9631 Cov.: 32 AF XY: 0.208 AC XY: 15487 AN XY: 74414

African (AFR) AF: 0.668 AC: 27690 AN: 41450

American (AMR) AF: 0.0938 AC: 1435 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3470

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5180

South Asian (SAS) AF: 0.0951 AC: 459 AN: 4824

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10626

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0332 AC: 2256 AN: 68008

Other (OTH) AF: 0.168 AC: 354 AN: 2106

Alfa AF: 0.0961 Hom.: 3715

Bravo AF: 0.241

Asia WGS AF: 0.0940 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.30
PhyloP100		0.070
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: rs802571; hg19: chr7-145962186;