Genetic Variant SLC35A2:p.Ser201Arg (chrX-48904716-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005660.3(SLC35A2):c.1163+30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,208,841 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000037 ( 0 hom. 19 hem. )

Consequence

SLC35A2
NM_005660.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.740

Publications

0 publications found

Variant links:

Genes affected

SLC35A2 (HGNC:11022): (solute carrier family 35 member A2) This gene encodes a member of the nucleotide-sugar transporter family. The encoded protein is a multi-pass membrane protein. It transports UDP-galactose from the cytosol into Golgi vesicles, where it serves as a glycosyl donor for the generation of glycans. Mutations in this gene cause congenital disorder of glycosylation type IIm (CDG2M). Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

SLC35A2 Gene-Disease associations (from GenCC):

SLC35A2-congenital disorder of glycosylation
Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

SLC35A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07229298).

BP6

Variant X-48904716-G-C is Benign according to our data. Variant chrX-48904716-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3772214.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 19 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A2	NM_005660.3 link	c.1163+30C>G		intron_variant	Intron 4 of 4	ENST00000247138.11	NP_005651.1	P78381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11 link	c.1163+30C>G		intron_variant	Intron 4 of 4	1	NM_005660.3	ENSP00000247138.5		P78381-1

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111561

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

182041

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.0000765

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:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000374

AC:

AN:

1097280

Hom.:

Cov.:

AF XY:

0.0000524

AC XY:

AN XY:

362658

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26383

American (AMR)

AF:

0.00

AC:

AN:

35194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19368

East Asian (EAS)

AF:

0.00

AC:

AN:

30199

South Asian (SAS)

AF:

0.00

AC:

AN:

54074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4133

European-Non Finnish (NFE)

AF:

0.0000475

AC:

AN:

841343

Other (OTH)

AF:

0.00

AC:

AN:

46073

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111561

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33771

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30681

American (AMR)

AF:

0.00

AC:

AN:

10578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3545

South Asian (SAS)

AF:

0.00

AC:

AN:

2673

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6099

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52937

Other (OTH)

AF:

0.00

AC:

AN:

1496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000595

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC35A2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.090

(source)

DANN

Benign

0.58

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.98

PhyloP100

-0.74

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.010

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.93

T;T

Polyphen

0.062

B;.

Vest4

0.13

MutPred

0.23

Gain of methylation at S201 (P = 0.0158);.;

MVP

0.043

ClinPred

0.032

GERP RS

-4.7

Mutation Taster

=99/1

polymorphism

(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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chrX-48904716-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over