NM_015080.4:c.3758-1228C>G

Variant names:

• chr11-64627780-G-C
• rs10792443
• NM_015080.4:c.3758-1228C>G

Variant summary

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

The NM_015080.4(NRXN2):​c.3758-1228C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,028 control chromosomes in the GnomAD database, including 23,502 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 0.51 (23502 hom., cov: 31)
• Consequence: NRXN2 NM_015080.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 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.3758-1228C>G		intron	N/A	NP_055895.1
	NRXN2	NM_138732.3		c.3637+2622C>G		intron	N/A	NP_620060.1
	NRXN2	NM_001376262.1		c.3758-1228C>G		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.3758-1228C>G		intron	N/A	ENSP00000265459.5
	NRXN2	ENST00000704782.1		c.3767-1228C>G		intron	N/A	ENSP00000516031.1
	NRXN2	ENST00000377559.7	TSL:1	c.3637+2622C>G		intron	N/A	ENSP00000366782.3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77286 AN: 151910 Hom.: 23506 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.508 AC: 77289 AN: 152028 Hom.: 23502 Cov.: 31 AF XY: 0.502 AC XY: 37328 AN XY: 74302

African (AFR) AF: 0.186 AC: 7706 AN: 41462

American (AMR) AF: 0.499 AC: 7629 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2363 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1172 AN: 5168

South Asian (SAS) AF: 0.581 AC: 2798 AN: 4816

European-Finnish (FIN) AF: 0.576 AC: 6087 AN: 10564

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47408 AN: 67954

Other (OTH) AF: 0.554 AC: 1168 AN: 2108

Alfa AF: 0.597 Hom.: 3714

Bravo AF: 0.488

Asia WGS AF: 0.385 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.67
PhyloP100		0.32
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: rs10792443; hg19: chr11-64395252;