Genetic Variant NM_001363118.2:c.1122C>T (chr8-144360710-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001363118.2(SLC52A2):c.1122C>T(p.Leu374Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000636 in 1,565,694 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 2 hom. )

Consequence

SLC52A2
NM_001363118.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: -0.657

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 8-144360710-C-T is Benign according to our data. Variant chr8-144360710-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 392275.

BP7

Synonymous conserved (PhyloP=-0.657 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000663 (96/144896) while in subpopulation NFE AF = 0.00116 (77/66244). AF 95% confidence interval is 0.000953. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 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	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC52A2	NM_001363118.2	MANE Select	c.1122C>T	p.Leu374Leu	synonymous	Exon 4 of 5	NP_001350047.1	Q9HAB3
SLC52A2	NM_001253815.2		c.1122C>T	p.Leu374Leu	synonymous	Exon 4 of 5	NP_001240744.1	Q9HAB3
SLC52A2	NM_001253816.2		c.1122C>T	p.Leu374Leu	synonymous	Exon 4 of 5	NP_001240745.1	Q9HAB3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC52A2	ENST00000643944.2	MANE Select	c.1122C>T	p.Leu374Leu	synonymous	Exon 4 of 5	ENSP00000496184.2	Q9HAB3
SLC52A2	ENST00000329994.7	TSL:1	c.1122C>T	p.Leu374Leu	synonymous	Exon 4 of 5	ENSP00000333638.2	Q9HAB3
SLC52A2	ENST00000675787.1		c.1111C>T	p.Arg371Cys	missense	Exon 3 of 4	ENSP00000502189.1	A0A6Q8PGB9

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

AN:

144896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000414

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000222

Gnomad FIN

AF:

0.000530

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000657

AC:

157

AN:

238862

AF XY:

0.000607

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000999

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.000511

GnomAD4 exome

AF:

0.000633

AC:

899

AN:

1420798

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

469

AN XY:

705776

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32862

American (AMR)

AF:

0.000136

AC:

AN:

43992

Ashkenazi Jewish (ASJ)

AF:

0.000197

AC:

AN:

25376

East Asian (EAS)

AF:

0.00

AC:

AN:

39168

South Asian (SAS)

AF:

0.0000589

AC:

AN:

84848

European-Finnish (FIN)

AF:

0.00107

AC:

AN:

45608

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000737

AC:

799

AN:

1084430

Other (OTH)

AF:

0.000561

AC:

AN:

58862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000663

AC:

AN:

144896

Hom.:

Cov.:

AF XY:

0.000639

AC XY:

AN XY:

70406

show subpopulations

African (AFR)

AF:

0.000155

AC:

AN:

38692

American (AMR)

AF:

0.000414

AC:

AN:

14490

Ashkenazi Jewish (ASJ)

AF:

0.000293

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

4936

South Asian (SAS)

AF:

0.000222

AC:

AN:

4498

European-Finnish (FIN)

AF:

0.000530

AC:

AN:

9428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

66244

Other (OTH)

AF:

0.00

AC:

AN:

1986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00138

Hom.:

Bravo

AF:

0.000548

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Brown-Vialetto-van Laere syndrome 2 (1)

Inborn genetic diseases (1)

SLC52A2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.3

(source)

DANN

Benign

0.71

PhyloP100

-0.66

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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