dbSNP rs34383175: SLC52A2:c.*19C>T (chr8-144361034-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.524

Publications

8 publications found

Variant links:

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

SLC52A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC52A2	NM_001363118.2	MANE Select	c.*19C>T	3_prime_UTR	Exon 5 of 5	NP_001350047.1	Q9HAB3
SLC52A2	NM_001253815.2		c.*19C>T	3_prime_UTR	Exon 5 of 5	NP_001240744.1	Q9HAB3
SLC52A2	NM_001253816.2		c.*19C>T	3_prime_UTR	Exon 5 of 5	NP_001240745.1	Q9HAB3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC52A2	ENST00000643944.2	MANE Select	c.*19C>T	3_prime_UTR	Exon 5 of 5	ENSP00000496184.2	Q9HAB3
SLC52A2	ENST00000329994.7	TSL:1	c.*19C>T	3_prime_UTR	Exon 5 of 5	ENSP00000333638.2	Q9HAB3
SLC52A2	ENST00000402965.5	TSL:2	c.*19C>T	3_prime_UTR	Exon 5 of 5	ENSP00000385961.1	Q9HAB3

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3617

AN:

152052

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0303

AC XY:

21828

AN XY:

721484

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2406

4812

7217

9623

12029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1444

2888

4332

5776

7220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0238

AC:

3617

AN:

152170

Hom.:

Cov.:

AF XY:

0.0225

AC XY:

1677

AN XY:

74390

show subpopulations

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:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0351

AC:

372

AN:

10604

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0367

AC:

2498

AN:

67978

Other (OTH)

AF:

0.0251

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

187

375

562

750

937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0295

Hom.:

Bravo

AF:

0.0219

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.99

(source)

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over