11-64648295-G-A

Position:

chr11-64648295-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015080.4(NRXN2):c.3327C>T(p.Gly1109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,614,120 control chromosomes in the GnomAD database, including 17,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1347 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16280 hom. )

Consequence

NRXN2
NM_015080.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0180

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:40416): (NRXN2 antisense RNA 1)

NRXN2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 11-64648295-G-A is Benign according to our data. Variant chr11-64648295-G-A is described in ClinVar as [Benign]. Clinvar id is 129835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.018 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN2	NM_015080.4 linkuse as main transcript	c.3327C>T	p.Gly1109=	synonymous_variant	17/23	ENST00000265459.11	NP_055895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN2	ENST00000265459.11 linkuse as main transcript	c.3327C>T	p.Gly1109=	synonymous_variant	17/23	5	NM_015080.4	ENSP00000265459	P4	Q9P2S2-1
NRXN2-AS1	ENST00000433606.1 linkuse as main transcript	n.180+1717G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17515

AN:

152152

Hom.:

1348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0299

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0888

Gnomad ASJ

AF:

0.0496

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.136

AC:

34185

AN:

251360

Hom.:

2627

AF XY:

0.139

AC XY:

18832

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.0887

Gnomad ASJ exome

AF:

0.0528

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.145

AC:

211729

AN:

1461850

Hom.:

16280

Cov.:

AF XY:

0.144

AC XY:

104907

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

Gnomad4 AMR exome

AF:

0.0865

Gnomad4 ASJ exome

AF:

0.0530

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.115

AC:

17508

AN:

152270

Hom.:

1347

Cov.:

AF XY:

0.119

AC XY:

8850

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0299

Gnomad4 AMR

AF:

0.0886

Gnomad4 ASJ

AF:

0.0496

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.242

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.136

Hom.:

2963

Bravo

AF:

0.102

Asia WGS

AF:

0.175

AC:

607

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2020	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

NRXN2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

This variant is classified as 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

-0.36

CADD

Benign

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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