chr7-147829814-C-T

Position:

• chr7-147829814-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000361727.8(CNTNAP2):​c.2099-73751C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 151,942 control chromosomes in the GnomAD database, including 44,481 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 0.76 (44481 hom., cov: 30)
• Consequence: CNTNAP2 ENST00000361727.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.2099-73751C>T		intron_variant		ENST00000361727.8	NP_054860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.2099-73751C>T		intron_variant		1	NM_014141.6	ENSP00000354778	P1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114648 AN: 151824 Hom.: 44433 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.755 AC: 114746 AN: 151942 Hom.: 44481 Cov.: 30 AF XY: 0.747 AC XY: 55457 AN XY: 74222

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.775

Alfa AF: 0.711 Hom.: 17752

Bravo AF: 0.771

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.28
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

Other links and lift over

dbSNP: rs851715; hg19: chr7-147526906;