rs6960319

Variant names:

• chr7-147561539-G-A
• rs6960319
• NM_014141.6:c.1778-599G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-147561539-G-A
• chr7-147561539-G-C

Variant summary

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

The NM_014141.6(CNTNAP2):​c.1778-599G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,922 control chromosomes in the GnomAD database, including 6,757 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 0.30 (6757 hom., cov: 33)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• 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

LOC107986721 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	NM_014141.6	MANE Select	c.1778-599G>A		intron	N/A	NP_054860.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP2	ENST00000361727.8	TSL:1 MANE Select	c.1778-599G>A		intron	N/A	ENSP00000354778.3
	CNTNAP2	ENST00000636870.1	TSL:5	n.1640-599G>A		intron	N/A
	CNTNAP2	ENST00000637825.1	TSL:5	n.1261-599G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44793 AN: 151804 Hom.: 6750 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.295 AC: 44822 AN: 151922 Hom.: 6757 Cov.: 33 AF XY: 0.289 AC XY: 21450 AN XY: 74238

African (AFR) AF: 0.310 AC: 12843 AN: 41418

American (AMR) AF: 0.219 AC: 3339 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1390 AN: 5160

South Asian (SAS) AF: 0.305 AC: 1468 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2839 AN: 10544

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20769 AN: 67930

Other (OTH) AF: 0.294 AC: 620 AN: 2110

Alfa AF: 0.258 Hom.: 1852

Bravo AF: 0.290

Asia WGS AF: 0.270 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.46
PhyloP100		0.15
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: rs6960319; hg19: chr7-147258631;