rs183139471

Variant names:

• chr19-45486231-C-G
• rs183139471
• NM_005619.5:c.1498-118G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-45486231-C-G
• chr19-45486231-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005619.5(RTN2):​c.1498-118G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 791,366 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (7 hom., cov: 32)
  • Exomes 𝑓: 0.011 (82 hom.)
• Consequence: RTN2 NM_005619.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55
• Publications: 2 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]

RTN2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 12

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• neuronopathy, distal hereditary motor, autosomal recessive 11, with spasticity

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-45486231-C-G is Benign according to our data. Variant chr19-45486231-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1326798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00903 (1375/152272) while in subpopulation AMR AF = 0.0156 (238/15296). AF 95% confidence interval is 0.0139. There are 7 homozygotes in GnomAd4. There are 625 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AD,AR gene

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.1498-118G>C		intron	N/A	NP_005610.1	O75298-1
	RTN2	NM_206900.3		c.1279-118G>C		intron	N/A	NP_996783.1	O75298-2
	RTN2	NM_206901.3		c.478-118G>C		intron	N/A	NP_996784.1	O75298-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN2	ENST00000245923.9	TSL:1 MANE Select	c.1498-118G>C		intron	N/A	ENSP00000245923.3	O75298-1
	RTN2	ENST00000344680.8	TSL:1	c.1279-118G>C		intron	N/A	ENSP00000345127.3	O75298-2
	RTN2	ENST00000430715.6	TSL:1	c.478-118G>C		intron	N/A	ENSP00000398178.1	O75298-3

Frequencies

GnomAD3 genomes AF: 0.00905 AC: 1377 AN: 152154 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0112 AC: 7142 AN: 639094 Hom.: 82 AF XY: 0.0106 AC XY: 3592 AN XY: 338538

African (AFR) AF: 0.00246 AC: 41 AN: 16644

American (AMR) AF: 0.0159 AC: 488 AN: 30780

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 199 AN: 18336

East Asian (EAS) AF: 0.0000306 AC: 1 AN: 32724

South Asian (SAS) AF: 0.000530 AC: 32 AN: 60410

European-Finnish (FIN) AF: 0.00365 AC: 174 AN: 47668

Middle Eastern (MID) AF: 0.0100 AC: 33 AN: 3298

European-Non Finnish (NFE) AF: 0.0145 AC: 5734 AN: 396638

Other (OTH) AF: 0.0135 AC: 440 AN: 32596

GnomAD4 genome AF: 0.00903 AC: 1375 AN: 152272 Hom.: 7 Cov.: 32 AF XY: 0.00839 AC XY: 625 AN XY: 74470

African (AFR) AF: 0.00258 AC: 107 AN: 41536

American (AMR) AF: 0.0156 AC: 238 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00255 AC: 27 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0134 AC: 910 AN: 68030

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0106 Hom.: 3

Bravo AF: 0.0105

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.34
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs183139471; hg19: chr19-45989489;