rs782501346

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_001363118.2(SLC52A2):c.897C>A(p.Ser299Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC52A2
NM_001363118.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.269

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: Likely_pathogenic. The variant received 8 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 10 uncertain in NM_001363118.2

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A2	NM_001363118.2 link	c.897C>A	p.Ser299Arg	missense_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.897C>A	p.Ser299Arg	missense_variant	Exon 3 of 5		NM_001363118.2	ENSP00000496184.2		Q9HAB3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246530

AF XY:

0.00000746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455732

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111962

Other (OTH)

AF:

0.00

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

D;D;.;D;D;D;D

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.073

FATHMM_MKL

Uncertain

0.86

M_CAP

Pathogenic

0.41

MetaRNN

Pathogenic

0.94

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.1

M;M;.;M;M;M;M

PhyloP100

0.27

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.1

D;D;D;D;D;D;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.0010

D;D;D;D;D;D;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;.

Polyphen

1.0

D;D;.;D;D;D;D

Vest4

0.85

MutPred

0.84

Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);.;Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);

MVP

0.63

MPC

0.57

ClinPred

0.97

GERP RS

0.75

Varity_R

0.86

gMVP

0.92

Mutation Taster

=36/64

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over