rs10500171

Positions:

• chr7-147183313-A-G
• chr7-147183313-A-T

Variant summary

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

The NM_014141.6(CNTNAP2):​c.1348+50804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,050 control chromosomes in the GnomAD database, including 21,513 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 0.52 (21513 hom., cov: 33)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP2	NM_014141.6	c.1348+50804A>G		intron_variant		ENST00000361727.8	NP_054860.1
CNTNAP2	XM_017011950.3	c.1348+50804A>G		intron_variant			XP_016867439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.1348+50804A>G		intron_variant		1	NM_014141.6	ENSP00000354778	P1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79663 AN: 151932 Hom.: 21489 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.524 AC: 79730 AN: 152050 Hom.: 21513 Cov.: 33 AF XY: 0.527 AC XY: 39169 AN XY: 74350

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.580

Alfa AF: 0.444 Hom.: 1991

Bravo AF: 0.511

Asia WGS AF: 0.656 AC: 2283 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.84

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: rs10500171; hg19: chr7-146880405;