19-45488817-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005619.5(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 NM_005619.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.283

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN2	NM_005619.5	c.1380+31T>C		intron_variant		ENST00000245923.9
RTN2	NM_206900.3	c.1161+31T>C		intron_variant
RTN2	NM_206901.3	c.360+31T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN2	ENST00000245923.9	c.1380+31T>C		intron_variant		1	NM_005619.5

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1620 AN: 152130 Hom.: 71 Cov.: 32

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

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.: 33 AF XY: 0.00496 AC XY: 3558 AN XY: 717346

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.: 74 Cov.: 32 AF XY: 0.0123 AC XY: 915 AN XY: 74422

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.: 9

Bravo AF: 0.0179

Asia WGS AF: 0.0220 AC: 77 AN: 3478

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

May 16, 2021

- -

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

Other links and lift over

dbSNP: rs3745822; hg19: chr19-45992075;