rs144906809

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_015080.4(NRXN2):c.2918+6G>A variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron

Scores

Splicing: ADA: 0.008299

Clinical Significance

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

Conservation

PhyloP100: 0.318

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 211704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN2	NM_015080.4 link	c.2918+6G>A		splice_region_variant, intron_variant	Intron 14 of 22	ENST00000265459.11	NP_055895.1	Q9P2S2-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NRXN2	ENST00000265459.11 link	c.2918+6G>A	splice_region_variant, intron_variant	Intron 14 of 22	5	NM_015080.4	ENSP00000265459.5	Q9P2S2-1
NRXN2	ENST00000704782.1 link	c.2927+6G>A	splice_region_variant, intron_variant	Intron 13 of 21			ENSP00000516031.1	A0A994J5C3
NRXN2	ENST00000704781.1 link	c.2927+6G>A	splice_region_variant, intron_variant	Intron 13 of 21			ENSP00000516029.1	A0A994J4N8

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

GnomAD2 exomes

AF:

0.00139

AC:

349

AN:

250896

AF XY:

0.00138

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 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

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00107

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

340

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000301

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000924

AC:

1027

AN:

1112002

Other (OTH)

AF:

0.00252

AC:

152

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

188

281

375

469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00112

AC:

171

AN:

152264

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41550

American (AMR)

AF:

0.000850

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

68018

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jun 25, 2019

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.32

Mutation Taster

=98/2

polymorphism

(source)

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

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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