rs10487937

chr7-146360798-C-A

Variant summary

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

The NM_014141.6(CNTNAP2):c.97+243825C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,048 control chromosomes in the GnomAD database, including 4,078 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 0.14 (4078 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP2	NM_014141.6	c.97+243825C>A		intron_variant		ENST00000361727.8
CNTNAP2	XM_017011950.3	c.97+243825C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.97+243825C>A		intron_variant		1	NM_014141.6	P1
CNTNAP2	ENST00000625365.2	c.97+243825C>A		intron_variant		5
CNTNAP2	ENST00000637150.1	n.26+243825C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21967 AN: 151930 Hom.: 4055 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0754

Gnomad EAS AF: 0.0287

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.145 AC: 22025 AN: 152048 Hom.: 4078 Cov.: 32 AF XY: 0.143 AC XY: 10638 AN XY: 74328

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.0754

Gnomad4 EAS AF: 0.0288

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.0640

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0716 Hom.: 354

Bravo AF: 0.160

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.68
Dann	Benign	0.60

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: rs10487937; hg19: chr7-146057890;