rs700273

Positions:

• chr7-146479288-G-T

Variant summary

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

The NM_014141.6(CNTNAP2):​c.98-294983G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,064 control chromosomes in the GnomAD database, including 25,172 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 0.53 (25172 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.98-294983G>T		intron_variant		ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.98-294983G>T		intron_variant			XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.98-294983G>T		intron_variant		1	NM_014141.6	ENSP00000354778	P1
CNTNAP2	ENST00000625365.2	c.98-294983G>T		intron_variant		5		ENSP00000485955
CNTNAP2	ENST00000637150.1	n.27-294983G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80868 AN: 151944 Hom.: 25111 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.533 AC: 80990 AN: 152064 Hom.: 25172 Cov.: 32 AF XY: 0.523 AC XY: 38854 AN XY: 74302

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.505

Alfa AF: 0.435 Hom.: 8963

Bravo AF: 0.566

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.26

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: rs700273; hg19: chr7-146176380;