rs10487920

Variant names:

• chr7-146760987-C-A
• rs10487920
• NM_014141.6:c.98-13284C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-146760987-C-A
• chr7-146760987-C-T

Variant summary

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

The NM_014141.6(CNTNAP2):​c.98-13284C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,962 control chromosomes in the GnomAD database, including 2,730 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 0.18 (2730 hom., cov: 31)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 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.98-13284C>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.98-13284C>A		intron	N/A	ENSP00000354778.3	Q9UHC6-1
	CNTNAP2	ENST00000625365.2	TSL:5	c.98-13284C>A		intron	N/A	ENSP00000485955.1	A0A0D9SES4
	CNTNAP2	ENST00000637150.1	TSL:5	n.27-13284C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27705 AN: 151844 Hom.: 2728 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.183 AC: 27735 AN: 151962 Hom.: 2730 Cov.: 31 AF XY: 0.187 AC XY: 13920 AN XY: 74272

African (AFR) AF: 0.174 AC: 7220 AN: 41454

American (AMR) AF: 0.133 AC: 2037 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 886 AN: 3462

East Asian (EAS) AF: 0.273 AC: 1402 AN: 5142

South Asian (SAS) AF: 0.292 AC: 1402 AN: 4808

European-Finnish (FIN) AF: 0.257 AC: 2716 AN: 10552

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.170 AC: 11554 AN: 67966

Other (OTH) AF: 0.185 AC: 389 AN: 2108

Alfa AF: 0.174 Hom.: 2928

Bravo AF: 0.170

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		0.13
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: rs10487920; hg19: chr7-146458079;