rs506338

chr11-64673448-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.1197+3545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,056 control chromosomes in the GnomAD database, including 23,762 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 (23762 hom., cov: 31)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN2	NM_015080.4	c.1197+3545A>G		intron_variant		ENST00000265459.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN2	ENST00000265459.11	c.1197+3545A>G		intron_variant		5	NM_015080.4	P4

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78543 AN: 151938 Hom.: 23765 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.517 AC: 78559 AN: 152056 Hom.: 23762 Cov.: 31 AF XY: 0.510 AC XY: 37910 AN XY: 74310

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.561

Alfa AF: 0.653 Hom.: 15319

Bravo AF: 0.498

Asia WGS AF: 0.389 AC: 1354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.6
Dann	Benign	0.79

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: rs506338; hg19: chr11-64440920;