chr19-45486105-G-A
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_005619.5(RTN2):c.1506C>T(p.Ile502=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
RTN2
NM_005619.5 synonymous
NM_005619.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.559
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 19-45486105-G-A is Benign according to our data. Variant chr19-45486105-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2069241.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.559 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000112 (17/152106) while in subpopulation AMR AF= 0.00111 (17/15252). AF 95% confidence interval is 0.000709. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTN2 | NM_005619.5 | c.1506C>T | p.Ile502= | synonymous_variant | 10/11 | ENST00000245923.9 | NP_005610.1 | |
RTN2 | NM_206900.3 | c.1287C>T | p.Ile429= | synonymous_variant | 9/10 | NP_996783.1 | ||
RTN2 | NM_206901.3 | c.486C>T | p.Ile162= | synonymous_variant | 6/7 | NP_996784.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTN2 | ENST00000245923.9 | c.1506C>T | p.Ile502= | synonymous_variant | 10/11 | 1 | NM_005619.5 | ENSP00000245923 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152106Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251330Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135838
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461734Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727172
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74282
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 03, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at