2-50465422-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001330078.2(NRXN1):c.3364+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,594,926 control chromosomes in the GnomAD database, including 78,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6000 hom., cov: 31)

Exomes 𝑓: 0.31 ( 72421 hom. )

Consequence

NRXN1
NM_001330078.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.110

Publications

9 publications found

Variant links:

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)

NRXN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-50465422-A-G is Benign according to our data. Variant chr2-50465422-A-G is described in ClinVar as [Benign]. Clinvar id is 93601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN1	NM_001330078.2 link	c.3364+20T>C		intron_variant	Intron 17 of 22	ENST00000401669.7	NP_001317007.1	E7ERL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7 link	c.3364+20T>C		intron_variant	Intron 17 of 22	5	NM_001330078.2	ENSP00000385017.2		E7ERL8

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40426

AN:

151610

Hom.:

5991

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.272

GnomAD2 exomes

AF:

0.324

AC:

74025

AN:

228348

AF XY:

0.327

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.404

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.446

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.311

AC:

449181

AN:

1443200

Hom.:

72421

Cov.:

AF XY:

0.315

AC XY:

225462

AN XY:

716454

show subpopulations

African (AFR)

AF:

0.151

AC:

5008

AN:

33062

American (AMR)

AF:

0.402

AC:

17127

AN:

42562

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

5611

AN:

25602

East Asian (EAS)

AF:

0.394

AC:

15396

AN:

39056

South Asian (SAS)

AF:

0.464

AC:

38627

AN:

83324

European-Finnish (FIN)

AF:

0.256

AC:

13490

AN:

52678

Middle Eastern (MID)

AF:

0.238

AC:

1362

AN:

5716

European-Non Finnish (NFE)

AF:

0.304

AC:

334595

AN:

1101514

Other (OTH)

AF:

0.301

AC:

17965

AN:

59686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

14244

28487

42731

56974

71218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.267

AC:

40470

AN:

151726

Hom.:

6000

Cov.:

AF XY:

0.272

AC XY:

20180

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.160

AC:

6629

AN:

41450

American (AMR)

AF:

0.344

AC:

5213

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3466

East Asian (EAS)

AF:

0.430

AC:

2199

AN:

5116

South Asian (SAS)

AF:

0.481

AC:

2316

AN:

4812

European-Finnish (FIN)

AF:

0.239

AC:

2528

AN:

10586

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20005

AN:

67822

Other (OTH)

AF:

0.274

AC:

576

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1460

2920

4381

5841

7301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.282

Hom.:

13005

Bravo

AF:

0.267

Asia WGS

AF:

0.439

AC:

1525

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 02, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Pitt-Hopkins-like syndrome 2

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.078

(source)

DANN

Benign

0.28

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-50465422-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over