rs985829

Variant names:

• chr7-147575589-T-A
• rs985829
• NM_014141.6:c.1897+13332T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-147575589-T-A
• chr7-147575589-T-G

Variant summary

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

The NM_014141.6(CNTNAP2):​c.1897+13332T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,116 control chromosomes in the GnomAD database, including 36,486 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 0.69 (36486 hom., cov: 28)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 1 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 = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.1897+13332T>A		intron_variant	Intron 12 of 23	ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.1897+13332T>A		intron_variant	Intron 12 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.1897+13332T>A		intron_variant	Intron 12 of 23	1	NM_014141.6	ENSP00000354778.3
CNTNAP2	ENST00000636870.1	n.1759+13332T>A		intron_variant	Intron 10 of 21	5
CNTNAP2	ENST00000637825.1	n.1380+13332T>A		intron_variant	Intron 9 of 13	5
CNTNAP2	ENST00000638117.1	n.1800+13332T>A		intron_variant	Intron 11 of 12	5

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104063 AN: 150994 Hom.: 36439 Cov.: 28

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.689 AC: 104165 AN: 151116 Hom.: 36486 Cov.: 28 AF XY: 0.684 AC XY: 50460 AN XY: 73774

African (AFR) AF: 0.807 AC: 33222 AN: 41146

American (AMR) AF: 0.713 AC: 10757 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1766 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3697 AN: 5090

South Asian (SAS) AF: 0.610 AC: 2930 AN: 4802

European-Finnish (FIN) AF: 0.593 AC: 6159 AN: 10378

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43450 AN: 67842

Other (OTH) AF: 0.677 AC: 1418 AN: 2094

Alfa AF: 0.663 Hom.: 4191

Bravo AF: 0.706

Asia WGS AF: 0.680 AC: 2369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.55
PhyloP100		0.30
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: rs985829; hg19: chr7-147272681;