chr19-45486215-G-T

Variant names:

• chr19-45486215-G-T
• rs73567088
• NM_005619.5:c.1498-102C>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.81).
• BP6: Variant 19-45486215-G-T is Benign according to our data. Variant chr19-45486215-G-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.1498-102C>A		intron	N/A	NP_005610.1	O75298-1
	RTN2	NM_206900.3		c.1279-102C>A		intron	N/A	NP_996783.1	O75298-2
	RTN2	NM_206901.3		c.478-102C>A		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.1498-102C>A		intron	N/A	ENSP00000245923.3	O75298-1
	RTN2	ENST00000344680.8	TSL:1	c.1279-102C>A		intron	N/A	ENSP00000345127.3	O75298-2
	RTN2	ENST00000430715.6	TSL:1	c.478-102C>A		intron	N/A	ENSP00000398178.1	O75298-3

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

African (AFR) AF: 0.0581 AC: 1211 AN: 20860

American (AMR) AF: 0.146 AC: 5029 AN: 34476

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 1114 AN: 20970

East Asian (EAS) AF: 0.140 AC: 4859 AN: 34826

South Asian (SAS) AF: 0.147 AC: 10013 AN: 68128

European-Finnish (FIN) AF: 0.0860 AC: 4248 AN: 49418

Middle Eastern (MID) AF: 0.0642 AC: 265 AN: 4130

European-Non Finnish (NFE) AF: 0.0806 AC: 46123 AN: 572524

Other (OTH) AF: 0.0912 AC: 3621 AN: 39720

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

African (AFR) AF: 0.0576 AC: 2392 AN: 41548

American (AMR) AF: 0.0974 AC: 1489 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 163 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1028 AN: 5176

South Asian (SAS) AF: 0.144 AC: 696 AN: 4824

European-Finnish (FIN) AF: 0.0968 AC: 1026 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0746 AC: 5076 AN: 68010

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0749 Hom.: 164

Bravo AF: 0.0813

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.81
CADD	Benign	3.4
DANN	Benign	0.72
PhyloP100		0.023
Mutation Taster		=100/0	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: rs73567088; hg19: chr19-45989473; COSMIC: COSV104368890; COSMIC: COSV104368890;