rs797045800

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP3BP6_Moderate

The NM_015080.4(NRXN2):c.3403C>T(p.Pro1135Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NRXN2
NM_015080.4 missense, splice_region

Scores

Splicing: ADA: 0.9817

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.13

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 Likely_benign. Variant got -1 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 11-64648219-G-A is Benign according to our data. Variant chr11-64648219-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211706.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRXN2	NM_015080.4 linkuse as main transcript	c.3403C>T	p.Pro1135Ser	missense_variant, splice_region_variant	17/23	ENST00000265459.11
NRXN2-AS1	XR_001748259.3 linkuse as main transcript	n.2587G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRXN2	ENST00000265459.11 linkuse as main transcript	c.3403C>T	p.Pro1135Ser	missense_variant, splice_region_variant	17/23	5	NM_015080.4	P4	Q9P2S2-1
NRXN2-AS1	ENST00000433606.1 linkuse as main transcript	n.180+1641G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 22, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.069

T;.;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.91

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.40

T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.7

L;.;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

D;D;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.012

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.99

D;D;D;.

Vest4

0.61

MutPred

0.44

Gain of catalytic residue at P1135 (P = 0.0083);.;Gain of catalytic residue at P1135 (P = 0.0083);.;

MVP

0.11

MPC

1.5

ClinPred

0.97

GERP RS

4.2

Varity_R

0.22

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.82

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