rs802200

Variant names:

• chr7-146408379-G-A
• rs802200
• NM_014141.6:c.97+291406G>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.97+291406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,866 control chromosomes in the GnomAD database, including 25,580 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 0.54 (25580 hom., cov: 31)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.97+291406G>A		intron_variant	Intron 1 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.97+291406G>A		intron_variant	Intron 1 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.97+291406G>A		intron_variant	Intron 1 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000625365.2	c.97+291406G>A		intron_variant	Intron 2 of 3	5		ENSP00000485955.1
CNTNAP2	ENST00000637150.1	n.26+291406G>A		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81388 AN: 151748 Hom.: 25520 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.537 AC: 81505 AN: 151866 Hom.: 25580 Cov.: 31 AF XY: 0.525 AC XY: 38974 AN XY: 74194

African (AFR) AF: 0.875 AC: 36277 AN: 41458

American (AMR) AF: 0.546 AC: 8319 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1449 AN: 3464

East Asian (EAS) AF: 0.278 AC: 1433 AN: 5156

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4808

European-Finnish (FIN) AF: 0.331 AC: 3485 AN: 10514

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27683 AN: 67908

Other (OTH) AF: 0.526 AC: 1108 AN: 2106

Alfa AF: 0.502 Hom.: 3606

Bravo AF: 0.573

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		0.40
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: rs802200; hg19: chr7-146105471;