NM_001363118.2(SLC52A2):c.401C>T (p.Pro134Leu) AND Brown-Vialetto-van Laere syndrome 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 20, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000799056.5

Allele description [Variation Report for NM_001363118.2(SLC52A2):c.401C>T (p.Pro134Leu)]

NM_001363118.2(SLC52A2):c.401C>T (p.Pro134Leu)

Gene:

SLC52A2:solute carrier family 52 member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_001363118.2(SLC52A2):c.401C>T (p.Pro134Leu)

HGVS:

NC_000008.11:g.144359893C>T
NG_032872.2:g.6337C>T
NM_001253815.2:c.401C>T
NM_001253816.2:c.401C>T
NM_001363118.2:c.401C>TMANE SELECT
NM_001363120.2:c.401C>T
NM_001363121.2:c.401C>T
NM_001363122.2:c.131-222C>T
NM_024531.5:c.401C>T
NP_001240744.1:p.Pro134Leu
NP_001240745.1:p.Pro134Leu
NP_001350047.1:p.Pro134Leu
NP_001350049.1:p.Pro134Leu
NP_001350050.1:p.Pro134Leu
NP_078807.1:p.Pro134Leu
NC_000008.10:g.145583553C>T
NG_032872.1:g.6337C>T
NM_024531.4:c.401C>T
NR_045600.2:n.861C>T

Protein change:

P134L

Links:

dbSNP: rs1447838904

NCBI 1000 Genomes Browser:

rs1447838904

Molecular consequence:

NM_001363122.2:c.131-222C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001253815.2:c.401C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001253816.2:c.401C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363118.2:c.401C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363120.2:c.401C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363121.2:c.401C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024531.5:c.401C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_045600.2:n.861C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Brown-Vialetto-van Laere syndrome 2
Synonyms:: Riboflavin transporter deficiency type 2
Identifiers:: MONDO: MONDO:0013867; MedGen: C3553538; Orphanet: 97229; OMIM: 614707

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000938703	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26669662, 28492532
SCV005329473	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000938703

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 24, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005329473

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 20, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2).

Guissart C, Drouot N, Oncel I, Leheup B, Gershoni-Barush R, Muller J, Ferdinandusse S, Larrieu L, Anheim M, Arslan EA, Claustres M, Tranchant C, Topaloglu H, Koenig M.

Eur J Hum Genet. 2016 Aug;24(8):1154-9. doi: 10.1038/ejhg.2015.259. Epub 2015 Dec 16.

PubMed [citation]

PMID:: 26669662
PMCID:: PMC4970675

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000938703.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC52A2 protein function. ClinVar contains an entry for this variant (Variation ID: 645041). This missense change has been observed in individual(s) with SLC52A2-related conditions (PMID: 26669662). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 134 of the SLC52A2 protein (p.Pro134Leu).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV005329473.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The observed missense variant c.401C>T(p.Pro134Leu) in SLC52A2 gene has been reported previously in homozygous state in two individuals with SLC52A2-related conditions (Guissart C, et al., 2016). The c.401C>T variant has 0.001% allele frequency in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. However, study on multiple affected individuals and functional impact of the variant is not available. Multiple lines of computational evidence (Polyphen, SIFT and Mutation Taster) predict a damaging effect on protein structure and function for this variant. The amino acid Proline at position 134 is changed to a Leucine changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Pro134Leu in SLC52A2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine