NM_005619.5:c.35-5C>T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005619.5(RTN2):c.35-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
RTN2
NM_005619.5 splice_region, intron
NM_005619.5 splice_region, intron
Scores
2
Splicing: ADA: 0.00002830
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.00200
Publications
0 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]
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ACMG classification
Classification was made for transcript
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=-0.7).
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RTN2 | NM_005619.5 | MANE Select | c.35-5C>T | splice_region intron | N/A | NP_005610.1 | |||
| RTN2 | NM_206900.3 | c.35-5C>T | splice_region intron | N/A | NP_996783.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RTN2 | ENST00000245923.9 | TSL:1 MANE Select | c.35-5C>T | splice_region intron | N/A | ENSP00000245923.3 | |||
| RTN2 | ENST00000344680.8 | TSL:1 | c.35-5C>T | splice_region intron | N/A | ENSP00000345127.3 | |||
| RTN2 | ENST00000591286.5 | TSL:1 | n.35-5C>T | splice_region intron | N/A | ENSP00000467863.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152194
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad OTH
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GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251264 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251264
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461680Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727152 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461680
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
727152
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86236
European-Finnish (FIN)
AF:
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
AC:
0
AN:
5664
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111962
Other (OTH)
AF:
AC:
0
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
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2
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0.00
0.20
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74354 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152194
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74354
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41444
American (AMR)
AF:
AC:
1
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5202
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68038
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
EpiCase
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EpiControl
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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