rs368022952
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_006946.4(SPTBN2):c.2262C>T(p.Ala754=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000717 in 1,603,770 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: 33)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
SPTBN2
NM_006946.4 synonymous
NM_006946.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -8.18
Genes affected
SPTBN2 (HGNC:11276): (spectrin beta, non-erythrocytic 2) Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 11-66705014-G-A is Benign according to our data. Variant chr11-66705014-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 448485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-8.18 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTBN2 | NM_006946.4 | c.2262C>T | p.Ala754= | synonymous_variant | 15/38 | ENST00000533211.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTBN2 | ENST00000533211.6 | c.2262C>T | p.Ala754= | synonymous_variant | 15/38 | 5 | NM_006946.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152232Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000137 AC: 33AN: 240284Hom.: 0 AF XY: 0.000152 AC XY: 20AN XY: 131470
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GnomAD4 exome AF: 0.0000675 AC: 98AN: 1451420Hom.: 0 Cov.: 36 AF XY: 0.0000816 AC XY: 59AN XY: 722614
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74506
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 25, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 15, 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