rs623022

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive spinocerebellar ataxia 14
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet
spinocerebellar ataxia type 5
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P

SPTBN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 305547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
SPTBN2	NM_006946.4 link	c.5340C>T	p.Asn1780Asn	synonymous_variant	Exon 27 of 38	ENST00000533211.6	NP_008877.2	O15020-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN2	ENST00000533211.6 link	c.5340C>T	p.Asn1780Asn	synonymous_variant	Exon 27 of 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

GnomAD2 exomes

AF:

0.0644

AC:

16051

AN:

249430

AF XY:

0.0644

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 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

African (AFR)

AF:

0.00789

AC:

264

AN:

33480

American (AMR)

AF:

0.0549

AC:

2454

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0263

AC:

688

AN:

26132

East Asian (EAS)

AF:

0.107

AC:

4260

AN:

39700

South Asian (SAS)

AF:

0.0664

AC:

5729

AN:

86256

European-Finnish (FIN)

AF:

0.135

AC:

6957

AN:

51480

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0506

AC:

56312

AN:

1111980

Other (OTH)

AF:

0.0545

AC:

3290

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

5360

10720

16081

21441

26801

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2102

4204

6306

8408

10510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0499

AC:

7603

AN:

152332

Hom.:

322

Cov.:

AF XY:

0.0539

AC XY:

4017

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00965

AC:

401

AN:

41572

American (AMR)

AF:

0.0542

AC:

829

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3472

East Asian (EAS)

AF:

0.114

AC:

590

AN:

5178

South Asian (SAS)

AF:

0.0752

AC:

363

AN:

4826

European-Finnish (FIN)

AF:

0.146

AC:

1552

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0542

AC:

3684

AN:

68030

Other (OTH)

AF:

0.0444

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

383

765

1148

1530

1913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0464

Hom.:

130

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

Apr 13, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jul 12, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SPTBN2-related disorder

Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

Autosomal dominant cerebellar ataxia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.8

(source)

DANN

Benign

0.83

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over