Variant chr2-50346870-GCGCCGCCGCCGCCGC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001330092.2(NRXN1):c.65_79delGCGGCGGCGGCGGCG(p.Gly22_Gly26del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00361 in 1,366,786 control chromosomes in the GnomAD database, including 340 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 302 hom. )

Consequence

NRXN1
NM_001330092.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 3.96

Variant links:

Genes affected

NRXN1 (HGNC:8008): (neurexin 1) This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]

NRXN1 links:

NRXN1 (HGNC:):

NRXN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-50346870-GCGCCGCCGCCGCCGC-G is Benign according to our data. Variant chr2-50346870-GCGCCGCCGCCGCCGC-G is described in ClinVar as [Benign]. Clinvar id is 287918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRXN1	NM_001330078.2 linkuse as main transcript	c.3365-109915_3365-109901delGCGGCGGCGGCGGCG		intron_variant		ENST00000401669.7	NP_001317007.1	E7ERL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRXN1	ENST00000401669.7 linkuse as main transcript	c.3365-109915_3365-109901delGCGGCGGCGGCGGCG		intron_variant		5	NM_001330078.2	ENSP00000385017.2		E7ERL8

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2202

AN:

150380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00696

Gnomad EAS

AF:

0.00412

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0000998

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000460

Gnomad OTH

AF:

0.0145

GnomAD3 exomes

AF:

0.00797

AC:

597

AN:

74950

Hom.:

196

AF XY:

0.00662

AC XY:

293

AN XY:

44242

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.0140

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.0000876

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00224

AC:

2726

AN:

1216306

Hom.:

302

AF XY:

0.00204

AC XY:

1216

AN XY:

594990

show subpopulations

Gnomad4 AFR exome

AF:

0.0679

Gnomad4 AMR exome

AF:

0.00750

Gnomad4 ASJ exome

AF:

0.00948

Gnomad4 EAS exome

AF:

0.00257

Gnomad4 SAS exome

AF:

0.000515

Gnomad4 FIN exome

AF:

0.000179

Gnomad4 NFE exome

AF:

0.000357

Gnomad4 OTH exome

AF:

0.00479

GnomAD4 genome

AF:

0.0147

AC:

2205

AN:

150480

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1038

AN XY:

73468

show subpopulations

Gnomad4 AFR

AF:

0.0488

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00696

Gnomad4 EAS

AF:

0.00414

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.0000998

Gnomad4 NFE

AF:

0.000460

Gnomad4 OTH

AF:

0.0144

Bravo

AF:

0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 02, 2016

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

NRXN1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 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

Splicing

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