rs490192

Variant names:

• chr11-64703897-G-A
• rs490192
• NM_015080.4:c.731-6105C>T

Variant summary

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

The NM_015080.4(NRXN2):​c.731-6105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,038 control chromosomes in the GnomAD database, including 10,544 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 (10544 hom., cov: 32)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• 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 Gene-Disease associations (from GenCC):

• autism

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015080.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	NM_015080.4	MANE Select	c.731-6105C>T		intron	N/A	NP_055895.1
	NRXN2	NM_138732.3		c.731-6105C>T		intron	N/A	NP_620060.1
	NRXN2	NM_001376262.1		c.731-6105C>T		intron	N/A	NP_001363191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	ENST00000265459.11	TSL:5 MANE Select	c.731-6105C>T		intron	N/A	ENSP00000265459.5
	NRXN2	ENST00000704782.1		c.731-6105C>T		intron	N/A	ENSP00000516031.1
	NRXN2	ENST00000377559.7	TSL:1	c.731-6105C>T		intron	N/A	ENSP00000366782.3

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49812 AN: 151920 Hom.: 10512 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.328 AC: 49886 AN: 152038 Hom.: 10544 Cov.: 32 AF XY: 0.329 AC XY: 24451 AN XY: 74310

African (AFR) AF: 0.595 AC: 24663 AN: 41456

American (AMR) AF: 0.241 AC: 3674 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 581 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2466 AN: 5162

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4818

European-Finnish (FIN) AF: 0.298 AC: 3148 AN: 10550

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

European-Non Finnish (NFE) AF: 0.200 AC: 13579 AN: 67990

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.281 Hom.: 1629

Bravo AF: 0.336

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.77
PhyloP100		-0.64
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: rs490192; hg19: chr11-64471369;