NM_001363118.2:c.835C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_001363118.2(SLC52A2):c.835C>T(p.Leu279Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,609,476 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SLC52A2
NM_001363118.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.321

Publications

0 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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 8-144360327-C-T is Benign according to our data. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.321 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A2	NM_001363118.2 link	c.835C>T	p.Leu279Leu	synonymous_variant	Exon 3 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.835C>T	p.Leu279Leu	synonymous_variant	Exon 3 of 5		NM_001363118.2	ENSP00000496184.2		Q9HAB3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000445

AC:

AN:

246936

AF XY:

0.0000596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1457230

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

725054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48840

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1111974

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41474

American (AMR)

AF:

0.0000654

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68036

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000617

Hom.:

Bravo

AF:

0.0000642

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brown-Vialetto-van Laere syndrome 2

Benign:1

Nov 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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. -

not provided

Benign:1

Mar 01, 2021

GeneDx

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

-0.46

CADD

Benign

5.5

(source)

DANN

Benign

0.79

PhyloP100

0.32

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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