19-45486231-C-G

Position:

• chr19-45486231-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN2	NM_005619.5	c.1498-118G>C		intron_variant		ENST00000245923.9	NP_005610.1
RTN2	NM_206900.3	c.1279-118G>C		intron_variant			NP_996783.1
RTN2	NM_206901.3	c.478-118G>C		intron_variant			NP_996784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN2	ENST00000245923.9	c.1498-118G>C		intron_variant		1	NM_005619.5	ENSP00000245923

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

Gnomad4 AFR exome AF: 0.00246

Gnomad4 AMR exome AF: 0.0159

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.0000306

Gnomad4 SAS exome AF: 0.000530

Gnomad4 FIN exome AF: 0.00365

Gnomad4 NFE exome AF: 0.0145

Gnomad4 OTH exome AF: 0.0135

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

Gnomad4 AFR AF: 0.00258

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0106 Hom.: 3

Bravo AF: 0.0105

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.34

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: rs183139471; hg19: chr19-45989489;