rs782078023

Variant names:

• chrX-48905290-C-T
• rs782078023
• NM_005660.3:c.619G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001282651.2(SLC35A2):​c.703G>A​(p.Val235Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,075,086 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000056 (0 hom. 2 hem.)
• Consequence: SLC35A2 NM_001282651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.65
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282651.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	NM_005660.3	MANE Select	c.619G>A	p.Val207Met	missense	Exon 4 of 5	NP_005651.1
	SLC35A2	NM_001282651.2		c.703G>A	p.Val235Met	missense	Exon 5 of 5	NP_001269580.1
	SLC35A2	NM_001282650.2		c.658G>A	p.Val220Met	missense	Exon 4 of 4	NP_001269579.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.619G>A	p.Val207Met	missense	Exon 4 of 5	ENSP00000247138.5
	SLC35A2	ENST00000376521.6	TSL:1	c.619G>A	p.Val207Met	missense	Exon 4 of 4	ENSP00000365704.1
	SLC35A2	ENST00000445167.7	TSL:1	c.427-398G>A		intron	N/A	ENSP00000402726.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00 AC: 0 AN: 139017 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000558 AC: 6 AN: 1075086 Hom.: 0 Cov.: 31 AF XY: 0.00000577 AC XY: 2 AN XY: 346914

African (AFR) AF: 0.00 AC: 0 AN: 26031

American (AMR) AF: 0.00 AC: 0 AN: 31679

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18674

East Asian (EAS) AF: 0.00 AC: 0 AN: 29356

South Asian (SAS) AF: 0.00 AC: 0 AN: 51145

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4083

European-Non Finnish (NFE) AF: 0.00000723 AC: 6 AN: 830423

Other (OTH) AF: 0.00 AC: 0 AN: 45151

GnomAD4 genome Cov.: 24

Alfa AF: 0.0000735 Hom.: 0

ExAC AF: 0.00000841 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	SLC35A2-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.67	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.6
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.22
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.069	T
Polyphen		0.96	D
Vest4		0.54
MutPred		0.52		Gain of stability (P = 0.1909)
MVP		0.18
MPC		1.8
ClinPred		0.85	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.62
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs782078023; hg19: chrX-48762567;