rs993715

Variant names:

• chr7-148025902-A-C
• rs993715
• NM_014141.6:c.2383+47913A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-148025902-A-C
• chr7-148025902-A-G
• chr7-148025902-A-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.2383+47913A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,042 control chromosomes in the GnomAD database, including 41,666 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 0.74 (41666 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.2383+47913A>C		intron_variant	Intron 15 of 23	ENST00000361727.8	NP_054860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.2383+47913A>C		intron_variant	Intron 15 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000627772.2	n.556+47913A>C		intron_variant	Intron 4 of 12	2
CNTNAP2	ENST00000636870.1	n.2245+47913A>C		intron_variant	Intron 13 of 21	5

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111668 AN: 151924 Hom.: 41613 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.735 AC: 111780 AN: 152042 Hom.: 41666 Cov.: 32 AF XY: 0.738 AC XY: 54814 AN XY: 74290

African (AFR) AF: 0.843 AC: 34940 AN: 41466

American (AMR) AF: 0.752 AC: 11490 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3468

East Asian (EAS) AF: 0.859 AC: 4426 AN: 5154

South Asian (SAS) AF: 0.640 AC: 3082 AN: 4818

European-Finnish (FIN) AF: 0.774 AC: 8180 AN: 10574

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45479 AN: 67978

Other (OTH) AF: 0.678 AC: 1431 AN: 2112

Alfa AF: 0.673 Hom.: 55655

Bravo AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.35
PhyloP100		-0.44
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: rs993715; hg19: chr7-147722994;