Variant rs139264192 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015080.4(NRXN2):c.3213C>G(p.Leu1071Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,614,202 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 12 hom. )

Consequence

NRXN2
NM_015080.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.711

Variant links:

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 links:

NRXN2-AS1 (HGNC:):

NRXN2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-64648804-G-C is Benign according to our data. Variant chr11-64648804-G-C is described in ClinVar as [Benign]. Clinvar id is 211705.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-64648804-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.711 with no splicing effect.

BS2

High AC in GnomAd4 at 301 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN2	NM_015080.4 linkuse as main transcript	c.3213C>G	p.Leu1071Leu	synonymous_variant	16/23	ENST00000265459.11	NP_055895.1	Q9P2S2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NRXN2	ENST00000265459.11 linkuse as main transcript	c.3213C>G	p.Leu1071Leu	synonymous_variant	16/23	5	NM_015080.4	ENSP00000265459.5	Q9P2S2-1
NRXN2	ENST00000704782.1 linkuse as main transcript	c.3222C>G	p.Leu1074Leu	synonymous_variant	15/22			ENSP00000516031.1	A0A994J5C3
NRXN2	ENST00000704781.1 linkuse as main transcript	c.3222C>G	p.Leu1074Leu	synonymous_variant	15/22			ENSP00000516029.1	A0A994J4N8

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00231

AC:

582

AN:

251458

Hom.:

AF XY:

0.00233

AC XY:

317

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.00333

Gnomad NFE exome

AF:

0.00324

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00263

AC:

3846

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1849

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000827

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.00265

Gnomad4 FIN exome

AF:

0.00352

Gnomad4 NFE exome

AF:

0.00287

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152318

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00297

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00250

Hom.:

Bravo

AF:

0.00182

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00229

EpiControl

AF:

0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 13, 2015

- -

NRXN2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over