rs144290224

Positions:

chr8-144360710-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001363118.2(SLC52A2):c.1122C>T(p.Leu374Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000636 in 1,565,694 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 2 hom. )

Consequence

SLC52A2
NM_001363118.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: -0.657

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 links:

SLC52A2 (HGNC:):

SLC52A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 8-144360710-C-T is Benign according to our data. Variant chr8-144360710-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 392275.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=5, Uncertain_significance=1}. Variant chr8-144360710-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.657 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000663 (96/144896) while in subpopulation NFE AF= 0.00116 (77/66244). AF 95% confidence interval is 0.000953. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC52A2	NM_001363118.2 linkuse as main transcript	c.1122C>T	p.Leu374Leu	synonymous_variant	4/5	ENST00000643944.2	NP_001350047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC52A2	ENST00000643944.2 linkuse as main transcript	c.1122C>T	p.Leu374Leu	synonymous_variant	4/5		NM_001363118.2	ENSP00000496184.2		Q9HAB3

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

AN:

144896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000414

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000222

Gnomad FIN

AF:

0.000530

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000657

AC:

157

AN:

238862

Hom.:

AF XY:

0.000607

AC XY:

AN XY:

130054

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000677

Gnomad FIN exome

AF:

0.000999

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.000511

GnomAD4 exome

AF:

0.000633

AC:

899

AN:

1420798

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

469

AN XY:

705776

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.000197

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000589

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.000737

Gnomad4 OTH exome

AF:

0.000561

GnomAD4 genome

AF:

0.000663

AC:

AN:

144896

Hom.:

Cov.:

AF XY:

0.000639

AC XY:

AN XY:

70406

show subpopulations

Gnomad4 AFR

AF:

0.000155

Gnomad4 AMR

AF:

0.000414

Gnomad4 ASJ

AF:

0.000293

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000222

Gnomad4 FIN

AF:

0.000530

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.000548

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	SLC52A2: BP4 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	Sep 27, 2020	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Leu374Leu in exon 4 of SLC52A2: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.12% (76/63972) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs144290224). -

SLC52A2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 14, 2020

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

Brown-Vialetto-van Laere syndrome 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2019

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

-0.62

CADD

Benign

7.3

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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