Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_001363118.2(SLC52A2):c.835C>T(p.Leu279Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,609,476 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 (★★).
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
Our verdict: Benign. The variant received -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 8-144360327-C-T is Benign according to our data. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144360327-C-T is described in CliVar as Likely_benign. Clinvar id is 382629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.321 with no splicing effect.
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. -