NM_017780.4(CHD7):c.4669A>G (p.Arg1557Gly) AND CHARGE syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 29, 2021
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:: RCV001321147.7

Allele description [Variation Report for NM_017780.4(CHD7):c.4669A>G (p.Arg1557Gly)]

NM_017780.4(CHD7):c.4669A>G (p.Arg1557Gly)

Gene:

CHD7:chromodomain helicase DNA binding protein 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q12.2

Genomic location:

Preferred name:

NM_017780.4(CHD7):c.4669A>G (p.Arg1557Gly)

HGVS:

NC_000008.11:g.60841871A>G
NG_007009.1:g.168092A>G
NM_001316690.1:c.1717-20358A>G
NM_017780.4:c.4669A>GMANE SELECT
NP_060250.2:p.Arg1557Gly
LRG_176:g.168092A>G
NC_000008.10:g.61754430A>G

Protein change:

R1557G

Links:

dbSNP: rs1804990594

NCBI 1000 Genomes Browser:

rs1804990594

Molecular consequence:

NM_001316690.1:c.1717-20358A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_017780.4:c.4669A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: CHARGE syndrome (CHARGE)
Synonyms:: CHARGE ASSOCIATION--COLOBOMA, HEART ANOMALY, CHOANAL ATRESIA, RETARDATION, GENITAL AND EAR ANOMALIES; Coloboma, heart anomaly, choanal atresia, retardation, genital and ear anomalies; CHARGE association; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008965; MedGen: C0265354; Orphanet: 138; OMIM: 214800

Recent activity

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Mus musculus F-box protein 3 (Fbxo3), transcript variant 3, mRNA
Mus musculus F-box protein 3 (Fbxo3), transcript variant 3, mRNA
gi|1243457563|ref|NM_001355504.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001511966	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 29, 2021)	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

SCV001511966

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 29, 2021)

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, SCV001511966.4

#	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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of CHARGE syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 1557 of the CHD7 protein (p.Arg1557Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.

#	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

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