rs13225016

chr7-147559018-G-Achr7-147559018-G-C

Variant summary

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

The NM_014141.6(CNTNAP2):c.1778-3120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,128 control chromosomes in the GnomAD database, including 4,677 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 0.23 (4677 hom., cov: 33)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551

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]

LOC107986721 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP2	NM_014141.6	c.1778-3120G>A		intron_variant		ENST00000361727.8
LOC107986721	XR_001744999.2	n.142-397C>T		intron_variant, non_coding_transcript_variant
CNTNAP2	XM_017011950.3	c.1778-3120G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.1778-3120G>A		intron_variant		1	NM_014141.6	P1
CNTNAP2	ENST00000636870.1	n.1640-3120G>A		intron_variant, non_coding_transcript_variant		5
CNTNAP2	ENST00000637825.1	n.1261-3120G>A		intron_variant, non_coding_transcript_variant		5
CNTNAP2	ENST00000638117.1	n.1681-3120G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34415 AN: 152010 Hom.: 4673 Cov.: 33

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.226 AC: 34427 AN: 152128 Hom.: 4677 Cov.: 33 AF XY: 0.223 AC XY: 16591 AN XY: 74348

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.241

Alfa AF: 0.249 Hom.: 620

Bravo AF: 0.212

Asia WGS AF: 0.251 AC: 872 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	2.9
Dann	Benign	0.24

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: rs13225016; hg19: chr7-147256110;