rs199510198
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_020944.3(GBA2):c.2609G>A(p.Arg870Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R870R) has been classified as Likely benign.
Frequency
Consequence
NM_020944.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GBA2 | NM_020944.3 | c.2609G>A | p.Arg870Gln | missense_variant | 17/17 | ENST00000378103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GBA2 | ENST00000378103.7 | c.2609G>A | p.Arg870Gln | missense_variant | 17/17 | 1 | NM_020944.3 | P1 | |
GBA2 | ENST00000378094.4 | c.*132G>A | 3_prime_UTR_variant | 17/17 | 1 | ||||
GBA2 | ENST00000378088.1 | c.*293G>A | 3_prime_UTR_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152256Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000255 AC: 64AN: 250554Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135570
GnomAD4 exome AF: 0.000315 AC: 461AN: 1461804Hom.: 0 Cov.: 32 AF XY: 0.000314 AC XY: 228AN XY: 727206
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74380
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 870 of the GBA2 protein (p.Arg870Gln). This variant is present in population databases (rs199510198, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with GBA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 528000). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at