rs10244837

chr7-146778222-G-A

Variant summary

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

The NM_014141.6(CNTNAP2):c.208+3841G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,006 control chromosomes in the GnomAD database, including 16,525 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 0.42 (16525 hom., cov: 33)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP2	NM_014141.6	c.208+3841G>A		intron_variant		ENST00000361727.8
CNTNAP2	XM_017011950.3	c.208+3841G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.208+3841G>A		intron_variant		1	NM_014141.6	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63950 AN: 151888 Hom.: 16478 Cov.: 33

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.421 AC: 64055 AN: 152006 Hom.: 16525 Cov.: 33 AF XY: 0.421 AC XY: 31298 AN XY: 74290

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.401

Alfa AF: 0.373 Hom.: 1586

Bravo AF: 0.425

Asia WGS AF: 0.396 AC: 1375 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.6
Dann	Benign	0.39

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: rs10244837; hg19: chr7-146475314;