rs10487937

Variant names:

• chr7-146360798-C-A
• rs10487937
• NM_014141.6:c.97+243825C>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+243825C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,048 control chromosomes in the GnomAD database, including 4,078 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 0.14 (4078 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 0 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 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+243825C>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.97+243825C>A		intron	N/A	ENSP00000354778.3	Q9UHC6-1
	CNTNAP2	ENST00000625365.2	TSL:5	c.97+243825C>A		intron	N/A	ENSP00000485955.1	A0A0D9SES4
	CNTNAP2	ENST00000637150.1	TSL:5	n.26+243825C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21967 AN: 151930 Hom.: 4055 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0754

Gnomad EAS AF: 0.0287

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.145 AC: 22025 AN: 152048 Hom.: 4078 Cov.: 32 AF XY: 0.143 AC XY: 10638 AN XY: 74328

African (AFR) AF: 0.431 AC: 17852 AN: 41390

American (AMR) AF: 0.0729 AC: 1114 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0754 AC: 261 AN: 3460

East Asian (EAS) AF: 0.0288 AC: 149 AN: 5172

South Asian (SAS) AF: 0.0417 AC: 201 AN: 4822

European-Finnish (FIN) AF: 0.0640 AC: 678 AN: 10594

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.0210 AC: 1430 AN: 68016

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.0807 Hom.: 430

Bravo AF: 0.160

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.68
DANN	Benign	0.60
PhyloP100		-0.67
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: rs10487937; hg19: chr7-146057890;