rs11820322

Variant names:

• chr11-64645419-C-T
• rs11820322
• NM_015080.4:c.3403+2800G>A

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+2800G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 151,904 control chromosomes in the GnomAD database, including 1,150 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 0.10 (1150 hom., cov: 31)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 7 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN2	NM_015080.4	c.3403+2800G>A		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+2800G>A		intron_variant	Intron 17 of 22	5	NM_015080.4	ENSP00000265459.5
NRXN2	ENST00000704782.1	c.3412+2800G>A		intron_variant	Intron 16 of 21			ENSP00000516031.1
NRXN2	ENST00000704781.1	c.3412+2800G>A		intron_variant	Intron 16 of 21			ENSP00000516029.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15553 AN: 151786 Hom.: 1150 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0471

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.102 AC: 15568 AN: 151904 Hom.: 1150 Cov.: 31 AF XY: 0.103 AC XY: 7657 AN XY: 74260

African (AFR) AF: 0.185 AC: 7655 AN: 41358

American (AMR) AF: 0.106 AC: 1627 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3466

East Asian (EAS) AF: 0.290 AC: 1489 AN: 5134

South Asian (SAS) AF: 0.0750 AC: 360 AN: 4798

European-Finnish (FIN) AF: 0.0555 AC: 587 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0471 AC: 3202 AN: 67970

Other (OTH) AF: 0.0863 AC: 182 AN: 2110

Alfa AF: 0.0727 Hom.: 1147

Bravo AF: 0.111

Asia WGS AF: 0.147 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		-0.17
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: rs11820322; hg19: chr11-64412891;