rs478607

Variant names:

• chr11-64710591-G-A
• rs478607
• NM_015080.4:c.730+2379C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-64710591-G-A
• chr11-64710591-G-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.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
• Publications: 32 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: Ambry Genetics, G2P
• 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 (SAS) allele frequency at 95% confidence interval = 0.84 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	NM_015080.4	MANE Select	c.730+2379C>T		intron	N/A	NP_055895.1	Q9P2S2-1
	NRXN2	NM_138732.3		c.730+2379C>T		intron	N/A	NP_620060.1	Q9P2S2-2
	NRXN2	NM_001376262.1		c.730+2379C>T		intron	N/A	NP_001363191.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN2	ENST00000265459.11	TSL:5 MANE Select	c.730+2379C>T		intron	N/A	ENSP00000265459.5	Q9P2S2-1
	NRXN2	ENST00000704782.1		c.730+2379C>T		intron	N/A	ENSP00000516031.1	A0A994J5C3
	NRXN2	ENST00000377559.7	TSL:1	c.730+2379C>T		intron	N/A	ENSP00000366782.3	Q9P2S2-2

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

African (AFR) AF: 0.453 AC: 18757 AN: 41408

American (AMR) AF: 0.850 AC: 12987 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3264 AN: 3468

East Asian (EAS) AF: 0.816 AC: 4219 AN: 5172

South Asian (SAS) AF: 0.862 AC: 4155 AN: 4822

European-Finnish (FIN) AF: 0.757 AC: 7995 AN: 10568

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57353 AN: 68006

Other (OTH) AF: 0.781 AC: 1650 AN: 2112

Alfa AF: 0.793 Hom.: 88217

Bravo AF: 0.728

Asia WGS AF: 0.788 AC: 2741 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	0.60
DANN	Benign	0.69
PhyloP100		-0.43
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: rs478607; hg19: chr11-64478063;