Genetic Variant SLC35A2:p.Ala187Ala (chrX-48905348-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005660.3(SLC35A2):c.561C>T(p.Ala187Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000717 in 1,185,535 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 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 0.00036 ( 0 hom., 15 hem., cov: 24)

Exomes 𝑓: 0.000041 ( 0 hom. 7 hem. )

Consequence

SLC35A2
NM_005660.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.27

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-48905348-G-A is Benign according to our data. Variant chrX-48905348-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 383300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.27 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 15 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005660.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC35A2	NM_005660.3	MANE Select	c.561C>T	p.Ala187Ala	synonymous	Exon 4 of 5	NP_005651.1
SLC35A2	NM_001282651.2		c.645C>T	p.Ala215Ala	synonymous	Exon 5 of 5	NP_001269580.1
SLC35A2	NM_001282650.2		c.600C>T	p.Ala200Ala	synonymous	Exon 4 of 4	NP_001269579.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.561C>T	p.Ala187Ala	synonymous	Exon 4 of 5	ENSP00000247138.5
SLC35A2	ENST00000376521.6	TSL:1	c.561C>T	p.Ala187Ala	synonymous	Exon 4 of 4	ENSP00000365704.1
SLC35A2	ENST00000445167.7	TSL:1	c.427-456C>T		intron	N/A	ENSP00000402726.2

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

113312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000562

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

134238

AF XY:

0.0000740

show subpopulations

Gnomad AFR exome

AF:

0.00138

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:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1072170

Hom.:

Cov.:

AF XY:

0.0000201

AC XY:

AN XY:

347682

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

26145

American (AMR)

AF:

0.0000335

AC:

AN:

29812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18779

East Asian (EAS)

AF:

0.00

AC:

AN:

29245

South Asian (SAS)

AF:

0.00

AC:

AN:

51030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4057

European-Non Finnish (NFE)

AF:

0.00000964

AC:

AN:

829935

Other (OTH)

AF:

0.000177

AC:

AN:

45135

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

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000362

AC:

AN:

113365

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

AN XY:

35519

show subpopulations

African (AFR)

AF:

0.00112

AC:

AN:

31297

American (AMR)

AF:

0.000184

AC:

AN:

10857

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.000279

AC:

AN:

3582

South Asian (SAS)

AF:

0.00

AC:

AN:

2825

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6329

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000562

AC:

AN:

53361

Other (OTH)

AF:

0.00

AC:

AN:

1551

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000427

Hom.:

Bravo

AF:

0.000472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 06, 2018

GeneDx

Significance:Likely 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.

Inborn genetic diseases

Benign:1

Dec 28, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

SLC35A2-congenital disorder of glycosylation

Benign:1

Dec 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.21

(source)

DANN

Benign

0.85

PhyloP100

-3.3

Mutation Taster

=100/0

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over