rs2052328

Variant names:

• chr2-50924225-A-C
• rs2052328
• NM_001330078.2:c.791-1538T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-50924225-A-C
• chr2-50924225-A-G
• chr2-50924225-A-T

Variant summary

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

The NM_001330078.2(NRXN1):​c.791-1538T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,696 control chromosomes in the GnomAD database, including 7,266 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 0.27 (7266 hom., cov: 33)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 1 publications found

Genes affected

NRXN1 (HGNC:8008): (neurexin 1) This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]

NRXN1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• chromosome 2p16.3 deletion syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Pitt-Hopkins-like syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autism

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330078.2. 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
	NRXN1	NM_001330078.2	MANE Select	c.791-1538T>G		intron	N/A	NP_001317007.1	Q9ULB1-5
	NRXN1	NM_001135659.3		c.890-1538T>G		intron	N/A	NP_001129131.1	Q9ULB1-3
	NRXN1	NM_001330093.2		c.788-1538T>G		intron	N/A	NP_001317022.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN1	ENST00000401669.7	TSL:5 MANE Select	c.791-1538T>G		intron	N/A	ENSP00000385017.2	Q9ULB1-5
	NRXN1	ENST00000404971.5	TSL:1	c.890-1538T>G		intron	N/A	ENSP00000385142.1	Q9ULB1-3
	NRXN1	ENST00000625672.2	TSL:1	c.791-1538T>G		intron	N/A	ENSP00000485887.1	Q9ULB1-2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40546 AN: 151578 Hom.: 7241 Cov.: 33

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.268 AC: 40628 AN: 151696 Hom.: 7266 Cov.: 33 AF XY: 0.275 AC XY: 20359 AN XY: 74134

African (AFR) AF: 0.450 AC: 18625 AN: 41424

American (AMR) AF: 0.325 AC: 4937 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3190 AN: 5120

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1898 AN: 10572

Middle Eastern (MID) AF: 0.207 AC: 60 AN: 290

European-Non Finnish (NFE) AF: 0.132 AC: 8934 AN: 67770

Other (OTH) AF: 0.270 AC: 568 AN: 2104

Alfa AF: 0.109 Hom.: 250

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.66
PhyloP100		0.26
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: rs2052328; hg19: chr2-51151363;