rs1557044030

Positions:

• chrX-48911497-CGATCCCGACCTCCGCCTCCCATGCGACTGCTCGGGCAGACTGTCTCACCCGCACTGGCGGTCCCCGGCTCCAATGCACCCGCGGAAACCGCCCCTGGCCCGGGCGCCGCGGTGGAACCACCAGCC-CT

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_005660.3(SLC35A2):​c.15_91+48delGGCTGGTGGTTCCACCGCGGCGCCCGGGCCAGGGGCGGTTTCCGCGGGTGCATTGGAGCCGGGGACCGCCAGTGCGGGTGAGACAGTCTGCCCGAGCAGTCGCATGGGAGGCGGAGGTCGGGATCinsA​(p.Ala6fs) variant causes a frameshift, splice donor, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: SLC35A2 NM_005660.3 frameshift, splice_donor, splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 0.689

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-48911498-GATCCCGACCTCCGCCTCCCATGCGACTGCTCGGGCAGACTGTCTCACCCGCACTGGCGGTCCCCGGCTCCAATGCACCCGCGGAAACCGCCCCTGGCCCGGGCGCCGCGGTGGAACCACCAGCC-T is Pathogenic according to our data. Variant chrX-48911498-GATCCCGACCTCCGCCTCCCATGCGACTGCTCGGGCAGACTGTCTCACCCGCACTGGCGGTCCCCGGCTCCAATGCACCCGCGGAAACCGCCCCTGGCCCGGGCGCCGCGGTGGAACCACCAGCC-T is described in ClinVar as [Pathogenic]. Clinvar id is 50363.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35A2	NM_005660.3	c.15_91+48delGGCTGGTGGTTCCACCGCGGCGCCCGGGCCAGGGGCGGTTTCCGCGGGTGCATTGGAGCCGGGGACCGCCAGTGCGGGTGAGACAGTCTGCCCGAGCAGTCGCATGGGAGGCGGAGGTCGGGATCinsA	p.Ala6fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	1/5	ENST00000247138.11	NP_005651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11	c.15_91+48delGGCTGGTGGTTCCACCGCGGCGCCCGGGCCAGGGGCGGTTTCCGCGGGTGCATTGGAGCCGGGGACCGCCAGTGCGGGTGAGACAGTCTGCCCGAGCAGTCGCATGGGAGGCGGAGGTCGGGATCinsA	p.Ala6fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	1/5	1	NM_005660.3	ENSP00000247138.5

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

SLC35A2-congenital disorder of glycosylation Pathogenic:2

Pathogenic, no assertion criteria provided	research	University of Washington Center for Mendelian Genomics, University of Washington	Nov 14, 2013	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 04, 2013	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557044030; hg19: chrX-48768775;