NM_032382.5(COG8):c.1682C>T (p.Thr561Met) AND COG8-congenital disorder of glycosylation

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 11, 2022
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:: RCV001317887.14

Allele description [Variation Report for NM_032382.5(COG8):c.1682C>T (p.Thr561Met)]

NM_032382.5(COG8):c.1682C>T (p.Thr561Met)

Genes:

LOC130059304:ATAC-STARR-seq lymphoblastoid silent region 7657 [Gene]
COG8:component of oligomeric golgi complex 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_032382.5(COG8):c.1682C>T (p.Thr561Met)

HGVS:

NC_000016.10:g.69330996G>A
NG_009013.1:g.13628C>T
NG_033043.1:g.4600C>T
NM_001379261.1:c.1823C>T
NM_001379262.1:c.1682C>T
NM_001379263.1:c.1721C>T
NM_001379264.1:c.1682C>T
NM_001379265.1:c.1582+1718C>T
NM_001379266.1:c.1414-1817C>T
NM_032382.5:c.1682C>TMANE SELECT
NP_001366190.1:p.Thr608Met
NP_001366191.1:p.Thr561Met
NP_001366192.1:p.Thr574Met
NP_001366193.1:p.Thr561Met
NP_115758.3:p.Thr561Met
NP_115758.3:p.Thr561Met
NC_000016.9:g.69364899G>A
NM_032382.4:c.1682C>T

Protein change:

T561M

Links:

dbSNP: rs143411142

NCBI 1000 Genomes Browser:

rs143411142

Molecular consequence:

NM_001379265.1:c.1582+1718C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001379266.1:c.1414-1817C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001379261.1:c.1823C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379262.1:c.1682C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379263.1:c.1721C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379264.1:c.1682C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_032382.5:c.1682C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: COG8-congenital disorder of glycosylation
Synonyms:: CDG IIh; Congenital disorder of glycosylation type 2H; COG8-CDG
Identifiers:: MONDO: MONDO:0012635; MedGen: C1970021; Orphanet: 95428; OMIM: 611182

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001508566	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 11, 2022)	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

SCV001508566

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 11, 2022)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001508566.3

#	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 threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 561 of the COG8 protein (p.Thr561Met). This variant is present in population databases (rs143411142, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with COG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 96219). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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: Nov 3, 2024

ClinVar

Relating variation to medicine