NM_017780.4(CHD7):c.5390G>C (p.Gly1797Ala) AND CHARGE syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Sep 24, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000282364.11

Allele description [Variation Report for NM_017780.4(CHD7):c.5390G>C (p.Gly1797Ala)]

NM_017780.4(CHD7):c.5390G>C (p.Gly1797Ala)

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.5390G>C (p.Gly1797Ala)

HGVS:

NC_000008.11:g.60849140G>C
NG_007009.1:g.175361G>C
NM_001316690.1:c.1717-13089G>C
NM_017780.4:c.5390G>CMANE SELECT
NP_060250.2:p.Gly1797Ala
LRG_176t1:c.5390G>C
LRG_176:g.175361G>C
NC_000008.10:g.61761699G>C
NM_017780.2:c.5390G>C
NM_017780.3:c.5390G>C

Protein change:

G1797A

Links:

dbSNP: rs780597592

NCBI 1000 Genomes Browser:

rs780597592

Molecular consequence:

NM_001316690.1:c.1717-13089G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_017780.4:c.5390G>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001414756	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22461308, 28492532
SCV003929454	Intergen, Intergen Genetics and Rare Diseases Diagnosis Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	unknown	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

SCV001414756

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 24, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003929454

Intergen, Intergen Genetics and Rare Diseases Diagnosis Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

unknown

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation update on the CHD7 gene involved in CHARGE syndrome.

Janssen N, Bergman JE, Swertz MA, Tranebjaerg L, Lodahl M, Schoots J, Hofstra RM, van Ravenswaaij-Arts CM, Hoefsloot LH.

Hum Mutat. 2012 Aug;33(8):1149-60. doi: 10.1002/humu.22086. Epub 2012 Apr 16. Review.

PubMed [citation]

PMID:: 22461308

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

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001414756.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant has not been reported in the literature in individuals affected with CHD7-related conditions. 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. This variant disrupts the p.Gly1797 amino acid residue in CHD7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22461308; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt CHD7 protein function. ClinVar contains an entry for this variant (Variation ID: 363466). This variant is present in population databases (rs780597592, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1797 of the CHD7 protein (p.Gly1797Ala).

#	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

From Intergen, Intergen Genetics and Rare Diseases Diagnosis Center, SCV003929454.1

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

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

Last Updated: Jul 15, 2024

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