chr19-45486231-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005619.5(RTN2):​c.1498-118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 639,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: RTN2 NM_005619.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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>A		intron	N/A	NP_005610.1	O75298-1
	RTN2	NM_206900.3		c.1279-118G>A		intron	N/A	NP_996783.1	O75298-2
	RTN2	NM_206901.3		c.478-118G>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.1498-118G>A		intron	N/A	ENSP00000245923.3	O75298-1
	RTN2	ENST00000344680.8	TSL:1	c.1279-118G>A		intron	N/A	ENSP00000345127.3	O75298-2
	RTN2	ENST00000430715.6	TSL:1	c.478-118G>A		intron	N/A	ENSP00000398178.1	O75298-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000313 AC: 2 AN: 639140 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 338564

African (AFR) AF: 0.00 AC: 0 AN: 16644

American (AMR) AF: 0.00 AC: 0 AN: 30786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18336

East Asian (EAS) AF: 0.00 AC: 0 AN: 32724

South Asian (SAS) AF: 0.00 AC: 0 AN: 60410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3298

European-Non Finnish (NFE) AF: 0.00000504 AC: 2 AN: 396678

Other (OTH) AF: 0.00 AC: 0 AN: 32596

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.26
DANN	Benign	0.41
PhyloP100		-1.6

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;