19-45486215-G-T

Position:

• chr19-45486215-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005619.5(RTN2):​c.1498-102C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 997,282 control chromosomes in the GnomAD database, including 4,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (582 hom., cov: 31)
  • Exomes 𝑓: 0.091 (3804 hom.)
• Consequence: RTN2 NM_005619.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0230

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-45486215-G-T is Benign according to our data. Variant chr19-45486215-G-T is described in ClinVar as [Benign]. Clinvar id is 677525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN2	NM_005619.5	c.1498-102C>A		intron_variant		ENST00000245923.9	NP_005610.1
RTN2	NM_206900.3	c.1279-102C>A		intron_variant			NP_996783.1
RTN2	NM_206901.3	c.478-102C>A		intron_variant			NP_996784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN2	ENST00000245923.9	c.1498-102C>A		intron_variant		1	NM_005619.5	ENSP00000245923

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12034 AN: 152112 Hom.: 577 Cov.: 31

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.0699

GnomAD4 exome AF: 0.0905 AC: 76483 AN: 845052 Hom.: 3804 AF XY: 0.0924 AC XY: 40481 AN XY: 438082

Gnomad4 AFR exome AF: 0.0581

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.0531

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.0860

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.0912

GnomAD4 genome AF: 0.0792 AC: 12057 AN: 152230 Hom.: 582 Cov.: 31 AF XY: 0.0830 AC XY: 6181 AN XY: 74438

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.0974

Gnomad4 ASJ AF: 0.0469

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0968

Gnomad4 NFE AF: 0.0746

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0763 Hom.: 102

Bravo AF: 0.0813

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.81
CADD	Benign	3.4
DANN	Benign	0.72

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: rs73567088; hg19: chr19-45989473; COSMIC: COSV104368890; COSMIC: COSV104368890;