rs1557044030

chrX-48911497-CGATCCCGACCTCCGCCTCCCATGCGACTGCTCGGGCAGACTGTCTCACCCGCACTGGCGGTCCCCGGCTCCAATGCACCCGCGGAAACCGCCCCTGGCCCGGGCGCCGCGGTGGAACCACCAGCC-CT

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_005660.3(SLC35A2):c.15_91+48delinsA variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: SLC35A2 NM_005660.3 splice_donor, splice_donor_5th_base, coding_sequence, 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 9 ACMG points.

• PVS1: Splicing variant, LoF is a know mechanism of disease,
• 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	UniProt
SLC35A2	NM_005660.3	c.15_91+48delinsA		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	1/5	ENST00000247138.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A2	ENST00000247138.11	c.15_91+48delinsA		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	1/5	1	NM_005660.3	P1

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