NM_005660.3:c.426+287_775del

Variant names:

• chrX-48905133-GCCACGGCGGTACCCTCAGCCCACCAGAGCCCCACCAGGCCCAGTGCTGTGCCGAAGAGGCCCAGTTGCAGGTTGCGCAGCCACACGGAGCCTGAGCTGCCTTTGAGGATCTTCTCAAAGTAGACACCTGCGAAGCCGGAGGAGAGACAGGAGGCCACGACGGCTGCCAGGCCTGCCCCAGGGTTCTGATCCAGTGGCCGTGGGCCTCCCCCACCGGCTTGCTGTGCCTGGACAATGGCGACGCCAGTGAAGAGGAGCAGCAGGGAGGCCCACTGCAGCCGGGAAAGGCTGCGATTCAGCATGAGCACGGAGAACAGCGCTGTGGTCAGGATCTTCAGCTGGTATGTCACCTGCGAGTGGCACGTGGAAGGCACTGAGGGCTGACCCTGGCCCCCAACAGGTGCACATGGGGGGCAGCACCCACTGTGGGCCCCCAGGCACAATGGAGGGACAGGGTGGGGGGTATGACAGCAAAAACAGCAAAAGGAGCCAGCCACTGGCCATTGGCTGAGCTGCAGCAAAACAGTTCTGAAGTCTCTCCCAGCAAGTGCACAAAAGGATGGCTGTGCCAAGAAGTCCACATCCCAATCCCATTTCCTGGCTGTGTGACTGGGGACAAAGCACTTGCCCTGTCTGAGCCCTGGCATCATCATCTATAAAAGATGGCTGAGGTATGGAAGTATCTTTGTGATGAGGGACTTGATACAAATGAATCAATAGCCACAACAATGTCAGCAAATACTTACATAGTGCTTACAATATATCAGTGTGGTTCTAGGCACTGCACGTGAATTCATTCATTTAATTCTCACAACACCATTCTGAAGTGAGCACCACTGTAAGCCCCAATTTAAAGGTGAGAAAACTAAGGCACAGAGAGGTTAGGTGACGTGCCCCAAAATCACACAGCTGGAAGGTAGCAGAGCTGAGATTTGAACCCAGACAGCCTGGCCCCAGAATCCAGGCTCTTTAA-G
• rs1557042824
• NM_005660.3:c.426+287_775del

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_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
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.16
• 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: 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 VariationId is 412239.Status of the report is criteria_provided_single_submitter, 1 stars.

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.426+287_775del	p.Val143fs	frameshift splice_acceptor splice_region intron	Exon 4 of 5	NP_005651.1	P78381-1
	SLC35A2	NM_001282651.2		c.510+287_859del	p.Val171fs	frameshift splice_acceptor splice_region intron	Exon 5 of 5	NP_001269580.1	P78381-4
	SLC35A2	NM_001282650.2		c.465+287_814del	p.Val156fs	frameshift splice_acceptor splice_region intron	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.426+287_775del	p.Val143fs	frameshift splice_acceptor splice_region intron	Exon 4 of 5	ENSP00000247138.5	P78381-1
	SLC35A2	ENST00000376521.6	TSL:1	c.426+287_775del	p.Val143fs	frameshift splice_acceptor splice_region intron	Exon 4 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000445167.7	TSL:1	c.426+287_427-242del		intron	N/A	ENSP00000402726.2	P78381-3

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	SLC35A2-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

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

Other links and lift over

dbSNP: rs1557042824; hg19: chrX-48762410;