rs1212146

Variant names:

• chr11-64645405-A-G
• rs1212146
• NM_015080.4:c.3403+2814T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015080.4(NRXN2):​c.3403+2814T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,736 control chromosomes in the GnomAD database, including 10,374 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 (10374 hom., cov: 31)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732
• Publications: 6 publications found

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]

NRXN2-AS1 (HGNC:40416): (NRXN2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.3403+2814T>C		intron_variant	Intron 17 of 22	ENST00000265459.11	NP_055895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN2	ENST00000265459.11	c.3403+2814T>C		intron_variant	Intron 17 of 22	5	NM_015080.4	ENSP00000265459.5
NRXN2	ENST00000704782.1	c.3412+2814T>C		intron_variant	Intron 16 of 21			ENSP00000516031.1
NRXN2	ENST00000704781.1	c.3412+2814T>C		intron_variant	Intron 16 of 21			ENSP00000516029.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49546 AN: 151618 Hom.: 10345 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.327 AC: 49619 AN: 151736 Hom.: 10374 Cov.: 31 AF XY: 0.328 AC XY: 24305 AN XY: 74154

African (AFR) AF: 0.586 AC: 24212 AN: 41320

American (AMR) AF: 0.239 AC: 3644 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3466

East Asian (EAS) AF: 0.501 AC: 2572 AN: 5130

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4810

European-Finnish (FIN) AF: 0.297 AC: 3137 AN: 10546

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13684 AN: 67908

Other (OTH) AF: 0.283 AC: 597 AN: 2106

Alfa AF: 0.229 Hom.: 2526

Bravo AF: 0.336

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.90
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1212146; hg19: chr11-64412877;