chr19-45485722-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005619.5(RTN2):c.1624G>T(p.Ala542Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005619.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTN2 | NM_005619.5 | c.1624G>T | p.Ala542Ser | missense_variant | 11/11 | ENST00000245923.9 | NP_005610.1 | |
RTN2 | NM_206900.3 | c.1405G>T | p.Ala469Ser | missense_variant | 10/10 | NP_996783.1 | ||
RTN2 | NM_206901.3 | c.604G>T | p.Ala202Ser | missense_variant | 7/7 | NP_996784.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTN2 | ENST00000245923.9 | c.1624G>T | p.Ala542Ser | missense_variant | 11/11 | 1 | NM_005619.5 | ENSP00000245923 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000440 AC: 11AN: 249912Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135216
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461716Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727160
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74326
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 542 of the RTN2 protein (p.Ala542Ser). This variant is present in population databases (rs745684949, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with RTN2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at