rs117156117

Variant names:

• chr19-45495123-T-C
• rs117156117
• NM_005619.5:c.51A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005619.5(RTN2):​c.51A>G​(p.Thr17Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,614,148 control chromosomes in the GnomAD database, including 405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (348 hom.)
• Consequence: RTN2 NM_005619.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.10
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 19-45495123-T-C is Benign according to our data. Variant chr19-45495123-T-C is described in ClinVar as Benign. ClinVar VariationId is 383326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005619.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN2	NM_005619.5	MANE Select	c.51A>G	p.Thr17Thr	synonymous	Exon 2 of 11	NP_005610.1
	RTN2	NM_206900.3		c.51A>G	p.Thr17Thr	synonymous	Exon 2 of 10	NP_996783.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN2	ENST00000245923.9	TSL:1 MANE Select	c.51A>G	p.Thr17Thr	synonymous	Exon 2 of 11	ENSP00000245923.3
	RTN2	ENST00000344680.8	TSL:1	c.51A>G	p.Thr17Thr	synonymous	Exon 2 of 10	ENSP00000345127.3
	RTN2	ENST00000591286.5	TSL:1	n.51A>G		non_coding_transcript_exon	Exon 2 of 10	ENSP00000467863.1

Frequencies

GnomAD3 genomes AF: 0.00943 AC: 1435 AN: 152180 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0525

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.0196 AC: 4929 AN: 251412 AF XY: 0.0156

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0534

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.00507 AC: 7405 AN: 1461850 Hom.: 348 Cov.: 33 AF XY: 0.00455 AC XY: 3311 AN XY: 727232

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.105 AC: 4710 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0442 AC: 1753 AN: 39700

South Asian (SAS) AF: 0.00391 AC: 337 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5742

European-Non Finnish (NFE) AF: 0.000154 AC: 171 AN: 1112002

Other (OTH) AF: 0.00631 AC: 381 AN: 60390

GnomAD4 genome AF: 0.00945 AC: 1439 AN: 152298 Hom.: 57 Cov.: 32 AF XY: 0.0106 AC XY: 792 AN XY: 74454

African (AFR) AF: 0.00149 AC: 62 AN: 41572

American (AMR) AF: 0.0679 AC: 1038 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0522 AC: 271 AN: 5190

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68014

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00213 Hom.: 5

Bravo AF: 0.0161

Asia WGS AF: 0.0190 AC: 65 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		1.1
Mutation Taster		=295/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs117156117; hg19: chr19-45998381;