chr11-66687154-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_006946.4(SPTBN2):c.6736G>A(p.Val2246Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,866 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 Uncertain significance (★★).
Frequency
Consequence
NM_006946.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250838Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135724
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461604Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727140
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74392
ClinVar
Submissions by phenotype
not provided Uncertain:2
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
BP4 -
not specified Uncertain:1
- -
Inborn genetic diseases Uncertain:1
The c.6736G>A (p.V2246M) alteration is located in exon 35 (coding exon 34) of the SPTBN2 gene. This alteration results from a G to A substitution at nucleotide position 6736, causing the valine (V) at amino acid position 2246 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Spinocerebellar ataxia type 5 Uncertain:1
A heterozygous missense variation in exon 36 of the SPTBN2 gene that results in the amino acid substitution of Methionine for Valine at codon 2246 was detected. The observed variant c.6736G>A (p.Val2246Met) has not been reported in the 1000 genomes and has a minor allele frequency of 0.001% in the 1000 genomes database. The in silico prediction of the variant is damaging by LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at