rs623022

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006946.4(SPTBN2):c.5340C>T(p.Asn1780Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 1,612,232 control chromosomes in the GnomAD database, including 3,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 322 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2738 hom. )

Consequence

SPTBN2
NM_006946.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.113

Variant links:

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]

SPTBN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 11-66691509-G-A is Benign according to our data. Variant chr11-66691509-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 305547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66691509-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.113 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN2	NM_006946.4 linkuse as main transcript	c.5340C>T	p.Asn1780Asn	synonymous_variant	27/38	ENST00000533211.6	NP_008877.2	O15020-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN2	ENST00000533211.6 linkuse as main transcript	c.5340C>T	p.Asn1780Asn	synonymous_variant	27/38	5	NM_006946.4	ENSP00000432568.1		O15020-1

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7586

AN:

152214

Hom.:

316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00965

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0533

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0743

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0463

GnomAD3 exomes

AF:

0.0644

AC:

16051

AN:

249430

Hom.:

717

AF XY:

0.0644

AC XY:

8699

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.00849

Gnomad AMR exome

AF:

0.0544

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.0696

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.0566

Gnomad OTH exome

AF:

0.0639

GnomAD4 exome

AF:

0.0548

AC:

80029

AN:

1459900

Hom.:

2738

Cov.:

AF XY:

0.0553

AC XY:

40198

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.00789

Gnomad4 AMR exome

AF:

0.0549

Gnomad4 ASJ exome

AF:

0.0263

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.0664

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.0506

Gnomad4 OTH exome

AF:

0.0545

GnomAD4 genome

AF:

0.0499

AC:

7603

AN:

152332

Hom.:

322

Cov.:

AF XY:

0.0539

AC XY:

4017

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00965

Gnomad4 AMR

AF:

0.0542

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0752

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.0542

Gnomad4 OTH

AF:

0.0444

Alfa

AF:

0.0465

Hom.:

127

Bravo

AF:

0.0403

Asia WGS

AF:

0.123

AC:

427

AN:

3478

EpiCase

AF:

0.0446

EpiControl

AF:

0.0443

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 13, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

SPTBN2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 12, 2017

- -

Autosomal dominant cerebellar ataxia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.8

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over