rs1324262269

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BP6

The NM_015080.4(NRXN2):c.359A>C(p.Asp120Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000261 in 1,380,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NRXN2
NM_015080.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.91

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 Gene-Disease associations (from GenCC):

autism
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P
neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

NRXN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41313246).

BP6

Variant 11-64713341-T-G is Benign according to our data. Variant chr11-64713341-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 436059.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015080.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRXN2	NM_015080.4	MANE Select	c.359A>C	p.Asp120Ala	missense	Exon 2 of 23	NP_055895.1	Q9P2S2-1
NRXN2	NM_138732.3		c.359A>C	p.Asp120Ala	missense	Exon 2 of 20	NP_620060.1	Q9P2S2-2
NRXN2	NM_001376262.1		c.359A>C	p.Asp120Ala	missense	Exon 2 of 23	NP_001363191.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRXN2	ENST00000265459.11	TSL:5 MANE Select	c.359A>C	p.Asp120Ala	missense	Exon 2 of 23	ENSP00000265459.5	Q9P2S2-1
NRXN2	ENST00000704782.1		c.359A>C	p.Asp120Ala	missense	Exon 1 of 22	ENSP00000516031.1	A0A994J5C3
NRXN2	ENST00000377559.7	TSL:1	c.359A>C	p.Asp120Ala	missense	Exon 2 of 20	ENSP00000366782.3	Q9P2S2-2

Frequencies

GnomAD3 genomes

AF:

0.0000859

AC:

AN:

151326

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

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:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

23154

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000187

AC:

AN:

1229636

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

601670

show subpopulations

African (AFR)

AF:

0.0000823

AC:

AN:

24298

American (AMR)

AF:

0.000158

AC:

AN:

12644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17938

East Asian (EAS)

AF:

0.00

AC:

AN:

27080

South Asian (SAS)

AF:

0.0000709

AC:

AN:

56444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3644

European-Non Finnish (NFE)

AF:

0.0000129

AC:

AN:

1007294

Other (OTH)

AF:

0.0000397

AC:

AN:

50334

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

Exome 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

GnomAD4 genome

AF:

0.0000859

AC:

AN:

151326

Hom.:

Cov.:

AF XY:

0.0000947

AC XY:

AN XY:

73944

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

41230

American (AMR)

AF:

0.00

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000590

AC:

AN:

67806

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

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:

0.0000712

Hom.:

Bravo

AF:

0.0000642

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

Eigen

Benign

0.14

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.91

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.1

PhyloP100

3.9

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.42

Sift

Benign

0.087

Sift4G

Uncertain

0.035

Polyphen

0.77

Vest4

0.26

MutPred

0.46

Gain of sheet (P = 0.0125)

MVP

0.093

MPC

0.77

ClinPred

0.39

GERP RS

3.5

PromoterAI

0.0039

Neutral

(source)

Varity_R

0.30

gMVP

0.48

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over