19-45488378-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_005619.5(RTN2):c.1497+93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,361,936 control chromosomes in the GnomAD database, including 34,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3758 hom., cov: 32)
  • Exomes 𝑓: 0.22 (31160 hom.)
• Consequence: RTN2 NM_005619.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 19-45488378-G-C is Benign according to our data. Variant chr19-45488378-G-C is described in ClinVar as [Benign]. Clinvar id is 670893.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN2	NM_005619.5	c.1497+93C>G		intron_variant		ENST00000245923.9
RTN2	NM_206900.3	c.1278+93C>G		intron_variant
RTN2	NM_206901.3	c.477+93C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN2	ENST00000245923.9	c.1497+93C>G		intron_variant		1	NM_005619.5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32938 AN: 152046 Hom.: 3758 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.221 AC: 267135 AN: 1209772 Hom.: 31160 AF XY: 0.217 AC XY: 131358 AN XY: 604332

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.217 AC: 32961 AN: 152164 Hom.: 3758 Cov.: 32 AF XY: 0.221 AC XY: 16419 AN XY: 74378

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.191

Alfa AF: 0.119 Hom.: 204

Bravo AF: 0.207

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	1.6
Dann	Benign	0.81

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

Other links and lift over

dbSNP: rs1603; hg19: chr19-45991636; COSMIC: COSV55594272; COSMIC: COSV55594272;