rs13382584

Variant names:

• chr2-51020156-T-C
• rs13382584
• NM_001330078.2:c.772+7346A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-51020156-T-C
• chr2-51020156-T-G

Variant summary

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

The NM_001330078.2(NRXN1):​c.772+7346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,540 control chromosomes in the GnomAD database, including 5,882 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 (5882 hom., cov: 31)
• Consequence: NRXN1 NM_001330078.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 5 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: G2P, Ambry Genetics, 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN1	NM_001330078.2	c.772+7346A>G		intron_variant	Intron 2 of 22	ENST00000401669.7	NP_001317007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7	c.772+7346A>G		intron_variant	Intron 2 of 22	5	NM_001330078.2	ENSP00000385017.2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41269 AN: 151422 Hom.: 5886 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.272 AC: 41267 AN: 151540 Hom.: 5882 Cov.: 31 AF XY: 0.268 AC XY: 19824 AN XY: 74032

African (AFR) AF: 0.214 AC: 8839 AN: 41400

American (AMR) AF: 0.208 AC: 3167 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1135 AN: 3466

East Asian (EAS) AF: 0.175 AC: 898 AN: 5128

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4812

European-Finnish (FIN) AF: 0.300 AC: 3151 AN: 10506

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.327 AC: 22166 AN: 67730

Other (OTH) AF: 0.247 AC: 519 AN: 2102

Alfa AF: 0.296 Hom.: 10207

Bravo AF: 0.260

Asia WGS AF: 0.188 AC: 653 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.60
PhyloP100		-0.071
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: rs13382584; hg19: chr2-51247294;