Variant rs1557042824 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_005660.3(SLC35A2):c.426+287_775del variant causes a splice acceptor, coding sequence, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 23)

Consequence

SLC35A2
NM_005660.3 splice_acceptor, coding_sequence, intron

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.16

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

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/exons	MANE	Protein	UniProt
SLC35A2	NM_005660.3 linkuse as main transcript	c.426+287_775del		splice_acceptor_variant, coding_sequence_variant, intron_variant	4/5	ENST00000247138.11	NP_005651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11 linkuse as main transcript	c.426+287_775del		splice_acceptor_variant, coding_sequence_variant, intron_variant	4/5	1	NM_005660.3	ENSP00000247138	P1	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

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 17, 2017

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.