rs146292053

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001363118.2(SLC52A2):c.1089G>A(p.Pro363Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,604,502 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 56 hom. )

Consequence

SLC52A2
NM_001363118.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -8.89

Publications

3 publications found

Variant links:

Genes affected

SLC52A2 (HGNC:30224): (solute carrier family 52 member 2) This gene encodes a membrane protein which belongs to the riboflavin transporter family. In humans, riboflavin must be obtained by intestinal absorption because it cannot be synthesized by the body. The water-soluble vitamin riboflavin is processed to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which then act as intermediaries in many cellular metabolic reactions. Paralogous members of the riboflavin transporter gene family are located on chromosomes 17 and 20. Unlike other members of this family, this gene has higher expression in brain tissue than small intestine. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. Mutations in this gene have been associated with Brown-Vialetto-Van Laere syndrome 2 - an autosomal recessive progressive neurologic disorder characterized by deafness, bulbar dysfunction, and axial and limb hypotonia. [provided by RefSeq, Jul 2012]

SLC52A2 Gene-Disease associations (from GenCC):

Brown-Vialetto-van Laere syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

SLC52A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-144360677-G-A is Benign according to our data. Variant chr8-144360677-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 385698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.89 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00576 (876/152088) while in subpopulation NFE AF = 0.0068 (462/67942). AF 95% confidence interval is 0.00629. There are 11 homozygotes in GnomAd4. There are 494 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A2	NM_001363118.2 link	c.1089G>A	p.Pro363Pro	synonymous_variant	Exon 4 of 5	ENST00000643944.2	NP_001350047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A2	ENST00000643944.2 link	c.1089G>A	p.Pro363Pro	synonymous_variant	Exon 4 of 5		NM_001363118.2	ENSP00000496184.2		Q9HAB3

Frequencies

GnomAD3 genomes

AF:

0.00576

AC:

876

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0327

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00680

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00579

AC:

1405

AN:

242682

AF XY:

0.00565

show subpopulations

Gnomad AFR exome

AF:

0.000633

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.000508

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.0349

Gnomad NFE exome

AF:

0.00598

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00558

AC:

8111

AN:

1452414

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

3998

AN XY:

722708

show subpopulations

African (AFR)

AF:

0.000628

AC:

AN:

33464

American (AMR)

AF:

0.00126

AC:

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.000500

AC:

AN:

26008

East Asian (EAS)

AF:

0.000302

AC:

AN:

39682

South Asian (SAS)

AF:

0.00186

AC:

160

AN:

86122

European-Finnish (FIN)

AF:

0.0316

AC:

1444

AN:

45646

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00547

AC:

6081

AN:

1110890

Other (OTH)

AF:

0.00515

AC:

310

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

461

922

1382

1843

2304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<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:

0.00576

AC:

876

AN:

152088

Hom.:

Cov.:

AF XY:

0.00664

AC XY:

494

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41504

American (AMR)

AF:

0.00157

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5146

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0327

AC:

347

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00680

AC:

462

AN:

67942

Other (OTH)

AF:

0.00427

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

122

162

203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00641

Hom.:

Bravo

AF:

0.00314

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00475

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 08, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC52A2: BS2 -

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 19, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro363Pro in exon 4 of SLC52A2: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 3.40% (224/6584) o f Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs146292053). -

Brown-Vialetto-van Laere syndrome 2

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Jul 11, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.8

(source)

DANN

Benign

0.81

PhyloP100

-8.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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