NM_017780.4(CHD7):c.1870G>A (p.Val624Ile) AND CHARGE syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 19, 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:: RCV003860654.2

Allele description [Variation Report for NM_017780.4(CHD7):c.1870G>A (p.Val624Ile)]

NM_017780.4(CHD7):c.1870G>A (p.Val624Ile)

Genes:

LOC126860403:CDK7 strongly-dependent group 2 enhancer GRCh37_chr8:61693034-61694233 [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.1870G>A (p.Val624Ile)

HGVS:

NC_000008.11:g.60781204G>A
NG_007009.1:g.107425G>A
NG_084903.1:g.830G>A
NM_001316690.1:c.1716+154G>A
NM_017780.4:c.1870G>AMANE SELECT
NP_060250.2:p.Val624Ile
NP_060250.2:p.Val624Ile
LRG_176t1:c.1870G>A
LRG_176:g.107425G>A
LRG_176p1:p.Val624Ile
NC_000008.10:g.61693763G>A
NM_017780.2:c.1870G>A

Protein change:

V624I

Molecular consequence:

NM_001316690.1:c.1716+154G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_017780.4:c.1870G>A - 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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NADH dehydrogenase subunit 2, partial (mitochondrion) [Pytilia melba]
NADH dehydrogenase subunit 2, partial (mitochondrion) [Pytilia melba]
gi|1818982620|gb|QII14725.1|

Protein
NADH dehydrogenase subunit 2, partial (mitochondrion) [Gymnoris dentata]
NADH dehydrogenase subunit 2, partial (mitochondrion) [Gymnoris dentata]
gi|1131115693|gb|APU54322.1|

Protein
glyceraldehyde-3-phosphodehydrogenase, partial [Malimbus malimbicus]
glyceraldehyde-3-phosphodehydrogenase, partial [Malimbus malimbicus]
gi|2553043621|gb|WKW55235.1|

Protein
NADH dehydrogenase subunit 2, partial (mitochondrion) [Malimbus cassini]
NADH dehydrogenase subunit 2, partial (mitochondrion) [Malimbus cassini]
gi|1131115679|gb|APU54315.1|

Protein
Phytochemicals
Phytochemicals
A broad range of biologically active compounds which occur naturally in plants having important medicinal and nutritional properties.<br/>Year introduced: 2014

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004667443	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 19, 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

SCV004667443

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 19, 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, SCV004667443.1

#	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 valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 624 of the CHD7 protein (p.Val624Ile). 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 CHD7-related conditions. 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 not expected to disrupt CHD7 protein function with a negative predictive value of 95%. 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: Sep 29, 2024

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