NM_005660.3(SLC35A2):c.497G>A (p.Arg166Gln) AND SLC35A2-congenital disorder of glycosylation

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 3, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000802532.4

Allele description [Variation Report for NM_005660.3(SLC35A2):c.497G>A (p.Arg166Gln)]

NM_005660.3(SLC35A2):c.497G>A (p.Arg166Gln)

Gene:

SLC35A2:solute carrier family 35 member A2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_005660.3(SLC35A2):c.497G>A (p.Arg166Gln)

HGVS:

NC_000023.11:g.48905412C>T
NG_034300.1:g.11547G>A
NM_001032289.3:c.427-520G>A
NM_001042498.3:c.497G>A
NM_001282647.2:c.427-520G>A
NM_001282648.2:c.355-520G>A
NM_001282649.2:c.314G>A
NM_001282650.2:c.536G>A
NM_001282651.2:c.581G>A
NM_005660.3:c.497G>AMANE SELECT
NP_001035963.1:p.Arg166Gln
NP_001269578.1:p.Arg105Gln
NP_001269579.1:p.Arg179Gln
NP_001269580.1:p.Arg194Gln
NP_005651.1:p.Arg166Gln
NC_000023.10:g.48762689C>T
NM_001042498.2:c.497G>A

Protein change:

R105Q

Links:

dbSNP: rs374840868

NCBI 1000 Genomes Browser:

rs374840868

Molecular consequence:

NM_001032289.3:c.427-520G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001282647.2:c.427-520G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001282648.2:c.355-520G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001042498.3:c.497G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282649.2:c.314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282650.2:c.536G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282651.2:c.581G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005660.3:c.497G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: SLC35A2-congenital disorder of glycosylation
Synonyms:: CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIm; CDG IIm; CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIm, SOMATIC MOSAIC; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010478; MedGen: C3806688; Orphanet: 356961; OMIM: 300896

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000942368	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000942368

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000942368.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 166 of the SLC35A2 protein (p.Arg166Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SLC35A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 647909). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC35A2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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Relating variation to medicine