chr8-144360706-T-G

Variant names:

• chr8-144360706-T-G
• rs200245353
• NM_001363118.2:c.1118T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363118.2(SLC52A2):​c.1118T>G​(p.Val373Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,594,510 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 Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC52A2 NM_001363118.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.253
• Publications: 0 publications found

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, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2493631).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363118.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A2	NM_001363118.2	MANE Select	c.1118T>G	p.Val373Gly	missense	Exon 4 of 5	NP_001350047.1	Q9HAB3
	SLC52A2	NM_001253815.2		c.1118T>G	p.Val373Gly	missense	Exon 4 of 5	NP_001240744.1	Q9HAB3
	SLC52A2	NM_001253816.2		c.1118T>G	p.Val373Gly	missense	Exon 4 of 5	NP_001240745.1	Q9HAB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A2	ENST00000643944.2	MANE Select	c.1118T>G	p.Val373Gly	missense	Exon 4 of 5	ENSP00000496184.2	Q9HAB3
	SLC52A2	ENST00000329994.7	TSL:1	c.1118T>G	p.Val373Gly	missense	Exon 4 of 5	ENSP00000333638.2	Q9HAB3
	SLC52A2	ENST00000402965.5	TSL:2	c.1118T>G	p.Val373Gly	missense	Exon 4 of 5	ENSP00000385961.1	Q9HAB3

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 4 AN: 150038 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000444

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444472 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 718156

African (AFR) AF: 0.00 AC: 0 AN: 33324

American (AMR) AF: 0.00 AC: 0 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 85510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104194

Other (OTH) AF: 0.00 AC: 0 AN: 59796

GnomAD4 genome AF: 0.0000267 AC: 4 AN: 150038 Hom.: 0 Cov.: 33 AF XY: 0.0000410 AC XY: 3 AN XY: 73200

African (AFR) AF: 0.0000247 AC: 1 AN: 40520

American (AMR) AF: 0.00 AC: 0 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5076

South Asian (SAS) AF: 0.00 AC: 0 AN: 4730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000444 AC: 3 AN: 67596

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Brown-Vialetto-van Laere syndrome 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.52	D
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.25
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.015	B
Vest4		0.37
MVP		0.33
MPC		0.19
ClinPred		0.78	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.43
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200245353; hg19: chr8-145584366;