rs2074714

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014141.6(CNTNAP2):c.1897+89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,539,444 control chromosomes in the GnomAD database, including 334,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 34895 hom., cov: 33)

Exomes 𝑓: 0.66 ( 299705 hom. )

Consequence

CNTNAP2
NM_014141.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.57

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 7-147562346-A-G is Benign according to our data. Variant chr7-147562346-A-G is described in ClinVar as [Benign]. Clinvar id is 670633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP2	NM_014141.6 link	c.1897+89A>G		intron_variant	Intron 12 of 23	ENST00000361727.8	NP_054860.1	Q9UHC6-1A0A090N7T7B2RCH4
CNTNAP2	XM_017011950.3 link	c.1897+89A>G		intron_variant	Intron 12 of 13		XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNTNAP2	ENST00000361727.8 link	c.1897+89A>G	intron_variant	Intron 12 of 23	1	NM_014141.6	ENSP00000354778.3	Q9UHC6-1
CNTNAP2	ENST00000636870.1 link	n.1759+89A>G	intron_variant	Intron 10 of 21	5
CNTNAP2	ENST00000637825.1 link	n.1380+89A>G	intron_variant	Intron 9 of 13	5
CNTNAP2	ENST00000638117.1 link	n.1800+89A>G	intron_variant	Intron 11 of 12	5

Frequencies

GnomAD3 genomes

AF:

0.675

AC:

102669

AN:

151992

Hom.:

34852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.712

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.630

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.673

GnomAD4 exome

AF:

0.656

AC:

910184

AN:

1387334

Hom.:

299705

AF XY:

0.653

AC XY:

453692

AN XY:

694412

show subpopulations

Gnomad4 AFR exome

AF:

0.730

Gnomad4 AMR exome

AF:

0.726

Gnomad4 ASJ exome

AF:

0.633

Gnomad4 EAS exome

AF:

0.609

Gnomad4 SAS exome

AF:

0.620

Gnomad4 FIN exome

AF:

0.611

Gnomad4 NFE exome

AF:

0.658

Gnomad4 OTH exome

AF:

0.661

GnomAD4 genome

AF:

0.676

AC:

102765

AN:

152110

Hom.:

34895

Cov.:

AF XY:

0.671

AC XY:

49852

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.729

Gnomad4 AMR

AF:

0.718

Gnomad4 ASJ

AF:

0.618

Gnomad4 EAS

AF:

0.626

Gnomad4 SAS

AF:

0.630

Gnomad4 FIN

AF:

0.594

Gnomad4 NFE

AF:

0.656

Gnomad4 OTH

AF:

0.673

Alfa

AF:

0.668

Hom.:

5610

Bravo

AF:

0.688

Asia WGS

AF:

0.637

AC:

2218

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.46

DANN

Benign

0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over