rs971818

Variant names:

• chr7-147506105-G-A
• rs971818
• NM_014141.6:c.1777+20064G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-147506105-G-A
• chr7-147506105-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.1777+20064G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,028 control chromosomes in the GnomAD database, including 37,939 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 (37939 hom., cov: 31)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.1777+20064G>A		intron_variant	Intron 11 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.1777+20064G>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.1777+20064G>A		intron_variant	Intron 11 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000636870.1	n.1639+20064G>A		intron_variant	Intron 9 of 21	5
CNTNAP2	ENST00000637825.1	n.1260+20064G>A		intron_variant	Intron 8 of 13	5
CNTNAP2	ENST00000638117.1	n.1680+20064G>A		intron_variant	Intron 10 of 12	5

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106919 AN: 151910 Hom.: 37916 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.704 AC: 106986 AN: 152028 Hom.: 37939 Cov.: 31 AF XY: 0.700 AC XY: 52030 AN XY: 74288

African (AFR) AF: 0.775 AC: 32159 AN: 41470

American (AMR) AF: 0.641 AC: 9800 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2951 AN: 5154

South Asian (SAS) AF: 0.556 AC: 2675 AN: 4814

European-Finnish (FIN) AF: 0.709 AC: 7480 AN: 10544

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47176 AN: 67984

Other (OTH) AF: 0.704 AC: 1485 AN: 2108

Alfa AF: 0.696 Hom.: 158595

Bravo AF: 0.703

Asia WGS AF: 0.615 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.71
PhyloP100		1.4
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: rs971818; hg19: chr7-147203197;