rs504915

Positions:

• chr11-64696613-T-A
• chr11-64696613-T-C

Variant summary

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

The NM_015080.4(NRXN2):​c.748+1162A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 150,306 control chromosomes in the GnomAD database, including 23,160 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 0.50 (23160 hom., cov: 28)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.748+1162A>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.748+1162A>T		intron_variant		5	NM_015080.4	ENSP00000265459	P4

Frequencies

GnomAD3 genomes AF: 0.504 AC: 75680 AN: 150192 Hom.: 23163 Cov.: 28

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.504 AC: 75683 AN: 150306 Hom.: 23160 Cov.: 28 AF XY: 0.498 AC XY: 36506 AN XY: 73318

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.554

Alfa AF: 0.587 Hom.: 3530

Bravo AF: 0.478

Asia WGS AF: 0.380 AC: 1323 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs504915; hg19: chr11-64464085;