NM_001111.5(ADAR):c.2662G>C (p.Gly888Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 20, 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:: RCV003808252.2

Allele description [Variation Report for NM_001111.5(ADAR):c.2662G>C (p.Gly888Arg)]

NM_001111.5(ADAR):c.2662G>C (p.Gly888Arg)

Genes:

LOC126805874:CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:154561176-154562375 [Gene]
ADAR:adenosine deaminase RNA specific [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_001111.5(ADAR):c.2662G>C (p.Gly888Arg)

HGVS:

NC_000001.11:g.154589763C>G
NG_011844.2:g.46798G>C
NG_082198.1:g.1164C>G
NM_001025107.3:c.1777G>C
NM_001111.5:c.2662G>CMANE SELECT
NM_001193495.2:c.1777G>C
NM_001365045.1:c.2689G>C
NM_001365046.1:c.1777G>C
NM_001365047.1:c.1777G>C
NM_001365048.1:c.1777G>C
NM_001365049.1:c.1699G>C
NM_015840.4:c.2584G>C
NM_015841.4:c.2527G>C
NP_001020278.1:p.Gly593Arg
NP_001102.3:p.Gly888Arg
NP_001180424.1:p.Gly593Arg
NP_001351974.1:p.Gly897Arg
NP_001351975.1:p.Gly593Arg
NP_001351976.1:p.Gly593Arg
NP_001351977.1:p.Gly593Arg
NP_001351978.1:p.Gly567Arg
NP_056655.3:p.Gly862Arg
NP_056656.3:p.Gly843Arg
LRG_1212t1:c.2662G>C
LRG_1212:g.46798G>C
LRG_1212p1:p.Gly888Arg
NC_000001.10:g.154562239C>G

Protein change:

G567R

Molecular consequence:

NM_001025107.3:c.1777G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001111.5:c.2662G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001193495.2:c.1777G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365045.1:c.2689G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365046.1:c.1777G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365047.1:c.1777G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365048.1:c.1777G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365049.1:c.1699G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015840.4:c.2584G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015841.4:c.2527G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Symmetrical dyschromatosis of extremities (DSH)
Synonyms:: Dyschromatosis symmetrica hereditaria 1; Dyschromatosis symmetrica hereditaria; Familial reticulate acropigmentation of Dohi; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007483; MedGen: C0406775; Orphanet: 41; OMIM: 127400

Name:: Aicardi-Goutieres syndrome 6 (AGS6)
Identifiers:: MONDO: MONDO:0014007; MedGen: C3539013; Orphanet: 51; OMIM: 615010

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
SCV004593609	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 20, 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

SCV004593609

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 20, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004593609.1

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

Description

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. 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 ADAR protein function. This variant has not been reported in the literature in individuals affected with ADAR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 888 of the ADAR protein (p.Gly888Arg).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine