rs6944808

Variant names:

• chr7-147555456-G-A
• rs6944808
• NM_014141.6:c.1778-6682G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-147555456-G-A
• chr7-147555456-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.1778-6682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,112 control chromosomes in the GnomAD database, including 37,269 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 0.70 (37269 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.1778-6682G>A		intron_variant	Intron 11 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.1778-6682G>A		intron_variant	Intron 11 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.1778-6682G>A		intron_variant	Intron 11 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000636870.1	n.1640-6682G>A		intron_variant	Intron 9 of 21	5
CNTNAP2	ENST00000637825.1	n.1261-6682G>A		intron_variant	Intron 8 of 13	5
CNTNAP2	ENST00000638117.1	n.1681-6682G>A		intron_variant	Intron 10 of 12	5

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106082 AN: 151994 Hom.: 37227 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.698 AC: 106175 AN: 152112 Hom.: 37269 Cov.: 32 AF XY: 0.692 AC XY: 51485 AN XY: 74366

African (AFR) AF: 0.749 AC: 31084 AN: 41494

American (AMR) AF: 0.736 AC: 11255 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2202 AN: 3470

East Asian (EAS) AF: 0.624 AC: 3222 AN: 5166

South Asian (SAS) AF: 0.625 AC: 3016 AN: 4826

European-Finnish (FIN) AF: 0.618 AC: 6531 AN: 10574

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46567 AN: 67982

Other (OTH) AF: 0.691 AC: 1462 AN: 2116

Alfa AF: 0.689 Hom.: 8956

Bravo AF: 0.709

Asia WGS AF: 0.638 AC: 2221 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.53
PhyloP100		-0.031
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: rs6944808; hg19: chr7-147252548;