rs478607

chr11-64710591-G-Achr11-64710591-G-C

Variant summary

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

The NM_015080.4(NRXN2):c.730+2379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,038 control chromosomes in the GnomAD database, including 43,236 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 0.73 (43236 hom., cov: 31)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN2	NM_015080.4	c.730+2379C>T		intron_variant		ENST00000265459.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN2	ENST00000265459.11	c.730+2379C>T		intron_variant		5	NM_015080.4	P4

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111392 AN: 151920 Hom.: 43219 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.733 AC: 111448 AN: 152038 Hom.: 43236 Cov.: 31 AF XY: 0.735 AC XY: 54588 AN XY: 74310

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.781

Alfa AF: 0.784 Hom.: 11424

Bravo AF: 0.728

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.60
Dann	Benign	0.69

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: rs478607; hg19: chr11-64478063;