rs782439562

Variant names:

• chrX-48904839-CCGGAGG-C
• rs782439562
• NM_005660.3:c.1064_1069delCCTCCG

Your query was ambiguous. Multiple possible variants found:

• chrX-48904839-CCGGAGG-C
• chrX-48904839-CCGGAGG-CCGGAGGCGGAGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM4 BP6_Very_Strong BS2

The NM_005660.3(SLC35A2):​c.1064_1069delCCTCCG​(p.Ala355_Ser356del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000479 in 1,209,989 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.000026 (0 hom. 5 hem.)
• Consequence: SLC35A2 NM_005660.3 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.44
• Publications: 0 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: Ambry Genetics, G2P, Orphanet, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005660.3.
• BP6: Variant X-48904839-CCGGAGG-C is Benign according to our data. Variant chrX-48904839-CCGGAGG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 412236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	NM_005660.3	MANE Select	c.1064_1069delCCTCCG	p.Ala355_Ser356del	disruptive_inframe_deletion	Exon 4 of 5	NP_005651.1	P78381-1
	SLC35A2	NM_001282651.2		c.1148_1153delCCTCCG	p.Ala383_Ser384del	disruptive_inframe_deletion	Exon 5 of 5	NP_001269580.1	P78381-4
	SLC35A2	NM_001282650.2		c.1103_1108delCCTCCG	p.Ala368_Ser369del	disruptive_inframe_deletion	Exon 4 of 4	NP_001269579.1	B4DE15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.1064_1069delCCTCCG	p.Ala355_Ser356del	disruptive_inframe_deletion	Exon 4 of 5	ENSP00000247138.5	P78381-1
	SLC35A2	ENST00000376521.6	TSL:1	c.1064_1069delCCTCCG	p.Ala355_Ser356del	disruptive_inframe_deletion	Exon 4 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000445167.7	TSL:1	c.474_479delCCTCCG	p.Leu159_Arg160del	disruptive_inframe_deletion	Exon 4 of 4	ENSP00000402726.2	P78381-3

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 29 AN: 112112 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000940

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: 0.0000496 AC: 9 AN: 181447 AF XY: 0.0000151

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.0000366

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: 0.0000264 AC: 29 AN: 1097821 Hom.: 0 AF XY: 0.0000138 AC XY: 5 AN XY: 363189

African (AFR) AF: 0.000871 AC: 23 AN: 26397

American (AMR) AF: 0.0000853 AC: 3 AN: 35174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40455

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841945

Other (OTH) AF: 0.0000434 AC: 2 AN: 46079

GnomAD4 genome AF: 0.000259 AC: 29 AN: 112168 Hom.: 0 Cov.: 23 AF XY: 0.000116 AC XY: 4 AN XY: 34342

African (AFR) AF: 0.000938 AC: 29 AN: 30927

American (AMR) AF: 0.00 AC: 0 AN: 10619

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6159

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53126

Other (OTH) AF: 0.00 AC: 0 AN: 1528

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000242

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	SLC35A2-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4
Mutation Taster		=187/13	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs782439562; hg19: chrX-48762116;