Variant 7-147395523-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014141.6(CNTNAP2):c.1499-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,298,102 control chromosomes in the GnomAD database, including 14,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1523 hom., cov: 32)

Exomes 𝑓: 0.14 ( 12892 hom. )

Consequence

CNTNAP2
NM_014141.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.198

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:

CNTNAP2 (HGNC:):

CNTNAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-147395523-C-T is Benign according to our data. Variant chr7-147395523-C-T is described in ClinVar as [Benign]. Clinvar id is 670795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP2	NM_014141.6 linkuse as main transcript	c.1499-86C>T		intron_variant		ENST00000361727.8	NP_054860.1	Q9UHC6-1A0A090N7T7B2RCH4
CNTNAP2	XM_017011950.3 linkuse as main transcript	c.1499-86C>T		intron_variant			XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8 linkuse as main transcript	c.1499-86C>T		intron_variant		1	NM_014141.6	ENSP00000354778.3		Q9UHC6-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19601

AN:

151892

Hom.:

1520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0753

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.139

AC:

159787

AN:

1146092

Hom.:

12892

AF XY:

0.140

AC XY:

81978

AN XY:

584200

show subpopulations

Gnomad4 AFR exome

AF:

0.0731

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.353

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.129

AC:

19619

AN:

152010

Hom.:

1523

Cov.:

AF XY:

0.134

AC XY:

9954

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0755

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.125

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.123

Hom.:

191

Bravo

AF:

0.129

Asia WGS

AF:

0.231

AC:

799

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

DANN

Benign

0.49

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