rs782168938

Variant names:

• chr8-144360829-C-A
• rs782168938
• NM_001363118.2:c.1152C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-144360829-C-A
• chr8-144360829-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001363118.2(SLC52A2):​c.1152C>A​(p.Gly384Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,460,946 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G384G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SLC52A2 NM_001363118.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.44
• 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, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10147607).
• BP6: Variant 8-144360829-C-A is Benign according to our data. Variant chr8-144360829-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1920851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.43 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A2	NM_001363118.2	MANE Select	c.1152C>A	p.Gly384Gly	synonymous	Exon 5 of 5	NP_001350047.1
	SLC52A2	NM_001253815.2		c.1152C>A	p.Gly384Gly	synonymous	Exon 5 of 5	NP_001240744.1
	SLC52A2	NM_001253816.2		c.1152C>A	p.Gly384Gly	synonymous	Exon 5 of 5	NP_001240745.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC52A2	ENST00000643944.2	MANE Select	c.1152C>A	p.Gly384Gly	synonymous	Exon 5 of 5	ENSP00000496184.2
	SLC52A2	ENST00000329994.7	TSL:1	c.1152C>A	p.Gly384Gly	synonymous	Exon 5 of 5	ENSP00000333638.2
	SLC52A2	ENST00000675787.1		c.1141C>A	p.Arg381Ser	missense	Exon 4 of 4	ENSP00000502189.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000440 AC: 11 AN: 249870 AF XY: 0.0000369

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: 0.0000978

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1460946 Hom.: 0 Cov.: 34 AF XY: 0.00000826 AC XY: 6 AN XY: 726774

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000824 AC: 10

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brown-Vialetto-van Laere syndrome 2 Benign:1

May 19, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	0.94
DANN	Benign	0.97
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.048	N
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.10	T
MetaSVM	Uncertain	0.035	D
PhyloP100		-2.4
PROVEAN	Benign	0.99	N
REVEL	Benign	0.12
Sift	Benign	0.25	T
Sift4G	Benign	0.66	T
Vest4		0.30
MutPred		0.45		Loss of MoRF binding (P = 0.0083)
MVP		0.40
ClinPred		0.075	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs782168938; hg19: chr8-145584489;