11-66705370-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_006946.4(SPTBN2):c.1906C>T(p.Arg636Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,612,298 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R636Q) has been classified as Benign.
Frequency
Consequence
NM_006946.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTBN2 | NM_006946.4 | c.1906C>T | p.Arg636Trp | missense_variant | 15/38 | ENST00000533211.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTBN2 | ENST00000533211.6 | c.1906C>T | p.Arg636Trp | missense_variant | 15/38 | 5 | NM_006946.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000103 AC: 25AN: 243510Hom.: 0 AF XY: 0.0000827 AC XY: 11AN XY: 133086
GnomAD4 exome AF: 0.0000473 AC: 69AN: 1460116Hom.: 0 Cov.: 36 AF XY: 0.0000454 AC XY: 33AN XY: 726382
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2019 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 26, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2022 | Unlikely to be causative of SPTBN2-related spinocerebellar ataxia (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at