dbSNP rs146079657: SLC35A2:p.Leu330Leu (chrX-48904919-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.990C>T(p.Leu330Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,208,994 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 361 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 0.00065 ( 0 hom., 27 hem., cov: 23)

Exomes 𝑓: 0.00089 ( 0 hom. 334 hem. )

Consequence

SLC35A2
NM_005660.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.292

Publications

4 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: Ambry Genetics, G2P, Orphanet, Illumina, PanelApp Australia, 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=-0.72).

BP6

Variant X-48904919-G-A is Benign according to our data. Variant chrX-48904919-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 383041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.292 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 27 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	UniProt
SLC35A2	NM_005660.3	MANE Select	c.990C>T	p.Leu330Leu	synonymous	Exon 4 of 5	NP_005651.1	P78381-1
SLC35A2	NM_001282651.2		c.1074C>T	p.Leu358Leu	synonymous	Exon 5 of 5	NP_001269580.1	P78381-4
SLC35A2	NM_001282650.2		c.1029C>T	p.Leu343Leu	synonymous	Exon 4 of 4	NP_001269579.1	B4DE15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.990C>T	p.Leu330Leu	synonymous	Exon 4 of 5	ENSP00000247138.5	P78381-1
SLC35A2	ENST00000376521.6	TSL:1	c.990C>T	p.Leu330Leu	synonymous	Exon 4 of 4	ENSP00000365704.1	P78381-2
SLC35A2	ENST00000445167.7	TSL:1	c.427-27C>T		intron	N/A	ENSP00000402726.2	P78381-3

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

112132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000648

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00199

GnomAD2 exomes

AF:

0.000567

AC:

102

AN:

180043

AF XY:

0.000695

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.000673

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000322

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.000672

GnomAD4 exome

AF:

0.000889

AC:

975

AN:

1096862

Hom.:

Cov.:

AF XY:

0.000922

AC XY:

334

AN XY:

362242

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26385

American (AMR)

AF:

0.000228

AC:

AN:

35123

Ashkenazi Jewish (ASJ)

AF:

0.000516

AC:

AN:

19362

East Asian (EAS)

AF:

0.00

AC:

AN:

30184

South Asian (SAS)

AF:

0.0000556

AC:

AN:

53958

European-Finnish (FIN)

AF:

0.000297

AC:

AN:

40451

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00106

AC:

895

AN:

841219

Other (OTH)

AF:

0.000999

AC:

AN:

46049

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.000651

AC:

AN:

112132

Hom.:

Cov.:

AF XY:

0.000788

AC XY:

AN XY:

34278

show subpopulations

African (AFR)

AF:

0.0000648

AC:

AN:

30871

American (AMR)

AF:

0.000189

AC:

AN:

10595

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3582

South Asian (SAS)

AF:

0.00

AC:

AN:

2730

European-Finnish (FIN)

AF:

0.000163

AC:

AN:

6146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00122

AC:

AN:

53124

Other (OTH)

AF:

0.00199

AC:

AN:

1510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000972

Hom.:

Bravo

AF:

0.000438

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLC35A2-congenital disorder of glycosylation (2)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.5

(source)

DANN

Benign

0.86

PhyloP100

-0.29

BranchPoint Hunter

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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