NM_001363118.2(SLC52A2):c.610C>A (p.Leu204Met) AND Brown-Vialetto-van Laere syndrome 2

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 20, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001361749.4

Allele description [Variation Report for NM_001363118.2(SLC52A2):c.610C>A (p.Leu204Met)]

NM_001363118.2(SLC52A2):c.610C>A (p.Leu204Met)

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.610C>A (p.Leu204Met)

HGVS:

NC_000008.11:g.144360102C>A
NG_032872.2:g.6546C>A
NM_001253815.2:c.610C>A
NM_001253816.2:c.610C>A
NM_001363118.2:c.610C>AMANE SELECT
NM_001363120.2:c.610C>A
NM_001363121.2:c.610C>A
NM_001363122.2:c.131-13C>A
NM_024531.5:c.610C>A
NP_001240744.1:p.Leu204Met
NP_001240745.1:p.Leu204Met
NP_001350047.1:p.Leu204Met
NP_001350049.1:p.Leu204Met
NP_001350050.1:p.Leu204Met
NP_078807.1:p.Leu204Met
NC_000008.10:g.145583762C>A
NR_045600.2:n.1070C>A

Protein change:

L204M

Links:

dbSNP: rs369895693

NCBI 1000 Genomes Browser:

rs369895693

Molecular consequence:

NM_001363122.2:c.131-13C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001253815.2:c.610C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001253816.2:c.610C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363118.2:c.610C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363120.2:c.610C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363121.2:c.610C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024531.5:c.610C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_045600.2:n.1070C>A - 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
SCV001557739	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 8, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005328673	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Sep 20, 2024)	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

SCV001557739

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 8, 2022)

germline

clinical testing

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

SCV005328673

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Sep 20, 2024)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001557739.2

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 204 of the SLC52A2 protein (p.Leu204Met). This variant is present in population databases (rs369895693, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SLC52A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1053410). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

#	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 3billion, SCV005328673.1

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

Description

The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine