chrX-48905133-GCCACGGCGGTACCCTCAGCCCACCAGAGCCCCACCAGGCCCAGTGCTGTGCCGAAGAGGCCCAGTTGCAGGTTGCGCAGCCACACGGAGCCTGAGCTGCCTTTGAGGATCTTCTCAAAGTAGACACCTGCGAAGCCGGAGGAGAGACAGGAGGCCACGACGGCTGCCAGGCCTGCCCCAGGGTTCTGATCCAGTGGCCGTGGGCCTCCCCCACCGGCTTGCTGTGCCTGGACAATGGCGACGCCAGTGAAGAGGAGCAGCAGGGAGGCCCACTGCAGCCGGGAAAGGCTGCGATTCAGCATGAGCACGGAGAACAGCGCTGTGGTCAGGATCTTCAGCTGGTATGTCACCTGCGAGTGGCACGTGGAAGGCACTGAGGGCTGACCCTGGCCCCCAACAGGTGCACATGGGGGGCAGCACCCACTGTGGGCCCCCAGGCACAATGGAGGGACAGGGTGGGGGGTATGACAGCAAAAACAGCAAAAGGAGCCAGCCACTGGCCATTGGCTGAGCTGCAGCAAAACAGTTCTGAAGTCTCTCCCAGCAAGTGCACAAAAGGATGGCTGTGCCAAGAAGTCCACATCCCAATCCCATTTCCTGGCTGTGTGACTGGGGACAAAGCACTTGCCCTGTCTGAGCCCTGGCATCATCATCTATAAAAGATGGCTGAGGTATGGAAGTATCTTTGTGATGAGGGACTTGATACAAATGAATCAATAGCCACAACAATGTCAGCAAATACTTACATAGTGCTTACAATATATCAGTGTGGTTCTAGGCACTGCACGTGAATTCATTCATTTAATTCTCACAACACCATTCTGAAGTGAGCACCACTGTAAGCCCCAATTTAAAGGTGAGAAAACTAAGGCACAGAGAGGTTAGGTGACGTGCCCCAAAATCACACAGCTGGAAGGTAGCAGAGCTGAGATTTGAACCCAGACAGCCTGGCCCCAGAATCCAGGCTCTTTAA-G

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate

The NM_005660.3(SLC35A2):c.426+287_775del(p.Val143fs) variant causes a frameshift, splice acceptor, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. V143V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 23)

Consequence

SLC35A2
NM_005660.3 frameshift, splice_acceptor, splice_region, intron

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.16

Publications

0 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: Illumina, Orphanet, G2P, Ambry Genetics, 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: Pathogenic. The variant received 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant X-48905133-GCCACGGCGGTACCCTCAGCCCACCAGAGCCCCACCAGGCCCAGTGCTGTGCCGAAGAGGCCCAGTTGCAGGTTGCGCAGCCACACGGAGCCTGAGCTGCCTTTGAGGATCTTCTCAAAGTAGACACCTGCGAAGCCGGAGGAGAGACAGGAGGCCACGACGGCTGCCAGGCCTGCCCCAGGGTTCTGATCCAGTGGCCGTGGGCCTCCCCCACCGGCTTGCTGTGCCTGGACAATGGCGACGCCAGTGAAGAGGAGCAGCAGGGAGGCCCACTGCAGCCGGGAAAGGCTGCGATTCAGCATGAGCACGGAGAACAGCGCTGTGGTCAGGATCTTCAGCTGGTATGTCACCTGCGAGTGGCACGTGGAAGGCACTGAGGGCTGACCCTGGCCCCCAACAGGTGCACATGGGGGGCAGCACCCACTGTGGGCCCCCAGGCACAATGGAGGGACAGGGTGGGGGGTATGACAGCAAAAACAGCAAAAGGAGCCAGCCACTGGCCATTGGCTGAGCTGCAGCAAAACAGTTCTGAAGTCTCTCCCAGCAAGTGCACAAAAGGATGGCTGTGCCAAGAAGTCCACATCCCAATCCCATTTCCTGGCTGTGTGACTGGGGACAAAGCACTTGCCCTGTCTGAGCCCTGGCATCATCATCTATAAAAGATGGCTGAGGTATGGAAGTATCTTTGTGATGAGGGACTTGATACAAATGAATCAATAGCCACAACAATGTCAGCAAATACTTACATAGTGCTTACAATATATCAGTGTGGTTCTAGGCACTGCACGTGAATTCATTCATTTAATTCTCACAACACCATTCTGAAGTGAGCACCACTGTAAGCCCCAATTTAAAGGTGAGAAAACTAAGGCACAGAGAGGTTAGGTGACGTGCCCCAAAATCACACAGCTGGAAGGTAGCAGAGCTGAGATTTGAACCCAGACAGCCTGGCCCCAGAATCCAGGCTCTTTAA-G is Pathogenic according to our data. Variant chrX-48905133-GCCACGGCGGTACCCTCAGCCCACCAGAGCCCCACCAGGCCCAGTGCTGTGCCGAAGAGGCCCAGTTGCAGGTTGCGCAGCCACACGGAGCCTGAGCTGCCTTTGAGGATCTTCTCAAAGTAGACACCTGCGAAGCCGGAGGAGAGACAGGAGGCCACGACGGCTGCCAGGCCTGCCCCAGGGTTCTGATCCAGTGGCCGTGGGCCTCCCCCACCGGCTTGCTGTGCCTGGACAATGGCGACGCCAGTGAAGAGGAGCAGCAGGGAGGCCCACTGCAGCCGGGAAAGGCTGCGATTCAGCATGAGCACGGAGAACAGCGCTGTGGTCAGGATCTTCAGCTGGTATGTCACCTGCGAGTGGCACGTGGAAGGCACTGAGGGCTGACCCTGGCCCCCAACAGGTGCACATGGGGGGCAGCACCCACTGTGGGCCCCCAGGCACAATGGAGGGACAGGGTGGGGGGTATGACAGCAAAAACAGCAAAAGGAGCCAGCCACTGGCCATTGGCTGAGCTGCAGCAAAACAGTTCTGAAGTCTCTCCCAGCAAGTGCACAAAAGGATGGCTGTGCCAAGAAGTCCACATCCCAATCCCATTTCCTGGCTGTGTGACTGGGGACAAAGCACTTGCCCTGTCTGAGCCCTGGCATCATCATCTATAAAAGATGGCTGAGGTATGGAAGTATCTTTGTGATGAGGGACTTGATACAAATGAATCAATAGCCACAACAATGTCAGCAAATACTTACATAGTGCTTACAATATATCAGTGTGGTTCTAGGCACTGCACGTGAATTCATTCATTTAATTCTCACAACACCATTCTGAAGTGAGCACCACTGTAAGCCCCAATTTAAAGGTGAGAAAACTAAGGCACAGAGAGGTTAGGTGACGTGCCCCAAAATCACACAGCTGGAAGGTAGCAGAGCTGAGATTTGAACCCAGACAGCCTGGCCCCAGAATCCAGGCTCTTTAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 412239.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A2	NM_005660.3 link	c.426+287_775del	p.Val143fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 4 of 5	ENST00000247138.11	NP_005651.1	P78381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11 link	c.426+287_775del	p.Val143fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 4 of 5	1	NM_005660.3	ENSP00000247138.5		P78381-1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SLC35A2-congenital disorder of glycosylation

Pathogenic:1

Feb 17, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is a gross deletion of the genomic region encompassing a portion of intron 3 and exon 4 of the SLC35A2 gene (c.426+287_775del). While this deletion is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated SLC35A2 protein lacking most or all of the residues encoded by exon 4 (~67% of the protein). While this particular variant has not been reported in the literature, several de novo missense and truncating variants in exon 4 have been reported in individuals affected with congenital disorders of glycosylation (PMID: 25262651, 24115232), suggesting that this region is important for protein function. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.2

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over