Variant chr19-45488817-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000245923.9(RTN2):c.1380+31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 1,597,320 control chromosomes in the GnomAD database, including 549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 74 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 475 hom. )

Consequence

RTN2
ENST00000245923.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.283

Variant links:

Genes affected

RTN2 (HGNC:10468): (reticulon 2) This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. Reticulon proteins also play an important role in the replication of positive-strand RNA (ssRNA) viruses. Mutations at this locus have been associated with autosomal dominant spastic paraplegia-12. [provided by RefSeq, Aug 2020]

RTN2 links:

PPM1N (HGNC:26845): (protein phosphatase, Mg2+/Mn2+ dependent 1N (putative)) Predicted to enable metal ion binding activity and protein serine/threonine phosphatase activity. Predicted to be involved in negative regulation of I-kappaB kinase/NF-kappaB signaling and positive regulation of canonical Wnt signaling pathway. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PPM1N links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-45488817-A-G is Benign according to our data. Variant chr19-45488817-A-G is described in ClinVar as [Benign]. Clinvar id is 1183266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RTN2	NM_005619.5 linkuse as main transcript	c.1380+31T>C	intron_variant	ENST00000245923.9	NP_005610.1
RTN2	NM_206900.3 linkuse as main transcript	c.1161+31T>C	intron_variant		NP_996783.1
RTN2	NM_206901.3 linkuse as main transcript	c.360+31T>C	intron_variant		NP_996784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN2	ENST00000245923.9 linkuse as main transcript	c.1380+31T>C		intron_variant		1	NM_005619.5	ENSP00000245923		O75298-1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1620

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0799

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0451

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0241

AC:

5251

AN:

218096

Hom.:

342

AF XY:

0.0189

AC XY:

2227

AN XY:

117590

show subpopulations

Gnomad AFR exome

AF:

0.000663

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.000649

Gnomad EAS exome

AF:

0.0460

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.00546

Gnomad NFE exome

AF:

0.000153

Gnomad OTH exome

AF:

0.0159

GnomAD4 exome

AF:

0.00548

AC:

7924

AN:

1445074

Hom.:

475

Cov.:

AF XY:

0.00496

AC XY:

3558

AN XY:

717346

show subpopulations

Gnomad4 AFR exome

AF:

0.000659

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.000234

Gnomad4 EAS exome

AF:

0.0391

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.00507

Gnomad4 NFE exome

AF:

0.0000977

Gnomad4 OTH exome

AF:

0.00559

GnomAD4 genome

AF:

0.0107

AC:

1636

AN:

152246

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

915

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.0805

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0457

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00459

Hom.:

Bravo

AF:

0.0179

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -
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

-0.85

CADD

Benign

6.4

DANN

Benign

0.60

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

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