Variant rs144906809 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_015080.4(NRXN2):c.2918+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,614,000 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 7 hom. )

Consequence

NRXN2
NM_015080.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.008299

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.318

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 11-64651249-C-T is Benign according to our data. Variant chr11-64651249-C-T is described in ClinVar as [Benign]. Clinvar id is 211704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64651249-C-T is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 171 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN2	NM_015080.4 linkuse as main transcript	c.2918+6G>A		splice_donor_region_variant, intron_variant		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.2918+6G>A		splice_donor_region_variant, intron_variant		5	NM_015080.4	ENSP00000265459	P4	Q9P2S2-1
NRXN2-AS1	ENST00000433606.1 linkuse as main transcript	n.180+4671C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00139

AC:

349

AN:

250896

Hom.:

AF XY:

0.00138

AC XY:

187

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00118

AC:

1722

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

873

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000924

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00112

AC:

171

AN:

152264

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00143

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00231

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 25, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0083

dbscSNV1_RF

Benign

0.17

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

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