8-144361034-C-T

Variant names:

• chr8-144361034-C-T
• rs34383175
• NM_001363118.2:c.*19C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001363118.2(SLC52A2):​c.*19C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,605,296 control chromosomes in the GnomAD database, including 871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (67 hom., cov: 33)
  • Exomes 𝑓: 0.031 (804 hom.)
• Consequence: SLC52A2 NM_001363118.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.524
• Publications: 8 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-144361034-C-T is Benign according to our data. Variant chr8-144361034-C-T is described in ClinVar as Benign. ClinVar VariationId is 257671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0238 (3617/152170) while in subpopulation NFE AF = 0.0367 (2498/67978). AF 95% confidence interval is 0.0355. There are 67 homozygotes in GnomAd4. There are 1677 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A2	NM_001363118.2	c.*19C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000643944.2	NP_001350047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A2	ENST00000643944.2	c.*19C>T		3_prime_UTR_variant	Exon 5 of 5		NM_001363118.2	ENSP00000496184.2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3617 AN: 152052 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.00597

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.0239 AC: 5960 AN: 248976 AF XY: 0.0238

Gnomad AFR exome AF: 0.00512

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0298

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0333

Gnomad NFE exome AF: 0.0366

Gnomad OTH exome AF: 0.0313

GnomAD4 exome AF: 0.0310 AC: 45096 AN: 1453126 Hom.: 804 Cov.: 33 AF XY: 0.0303 AC XY: 21828 AN XY: 721484

African (AFR) AF: 0.00480 AC: 160 AN: 33318

American (AMR) AF: 0.0141 AC: 629 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.0316 AC: 820 AN: 25970

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39480

South Asian (SAS) AF: 0.00425 AC: 366 AN: 86106

European-Finnish (FIN) AF: 0.0344 AC: 1790 AN: 51992

Middle Eastern (MID) AF: 0.0213 AC: 122 AN: 5740

European-Non Finnish (NFE) AF: 0.0359 AC: 39664 AN: 1105980

Other (OTH) AF: 0.0257 AC: 1541 AN: 59992

GnomAD4 genome AF: 0.0238 AC: 3617 AN: 152170 Hom.: 67 Cov.: 33 AF XY: 0.0225 AC XY: 1677 AN XY: 74390

African (AFR) AF: 0.00595 AC: 247 AN: 41506

American (AMR) AF: 0.0198 AC: 303 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0280 AC: 97 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4818

European-Finnish (FIN) AF: 0.0351 AC: 372 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0367 AC: 2498 AN: 67978

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.0295 Hom.: 19

Bravo AF: 0.0219

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Dec 31, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.99
DANN	Benign	0.66
PhyloP100		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs34383175; hg19: chr8-145584694;