rs490192

Positions:

• chr11-64703897-G-A

Variant summary

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

The NM_015080.4(NRXN2):​c.731-6105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,038 control chromosomes in the GnomAD database, including 10,544 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 0.33 (10544 hom., cov: 32)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

Genes affected

NRXN2 (HGNC:8009): (neurexin 2) This gene encodes a member of the neurexin gene family. The products of these genes function as cell adhesion molecules and receptors in the vertebrate nervous system. These genes utilize two promoters. The majority of transcripts are produced from the upstream promoter and encode alpha-neurexin isoforms while a smaller number of transcripts are produced from the downstream promoter and encode beta-neuresin isoforms. The alpha-neurexins contain epidermal growth factor-like (EGF-like) sequences and laminin G domains, and have been shown to interact with neurexophilins. The beta-neurexins lack EGF-like sequences and contain fewer laminin G domains than alpha-neurexins. Alternative splicing and the use of alternative promoters may generate thousands of transcript variants (PMID: 12036300, PMID: 11944992).[provided by RefSeq, Jun 2010]

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 = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.731-6105C>T		intron_variant		ENST00000265459.11	NP_055895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN2	ENST00000265459.11	c.731-6105C>T		intron_variant		5	NM_015080.4	ENSP00000265459	P4

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49812 AN: 151920 Hom.: 10512 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.328 AC: 49886 AN: 152038 Hom.: 10544 Cov.: 32 AF XY: 0.329 AC XY: 24451 AN XY: 74310

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.279

Alfa AF: 0.273 Hom.: 1489

Bravo AF: 0.336

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.77

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: rs490192; hg19: chr11-64471369;