NM_017780.4(CHD7):c.8672A>G (p.Asn2891Ser) AND CHARGE association

Clinical significance:Uncertain significance (Last evaluated: Oct 19, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_017780.4(CHD7):c.8672A>G (p.Asn2891Ser)]

NM_017780.4(CHD7):c.8672A>G (p.Asn2891Ser)

CHD7:chromodomain helicase DNA binding protein 7 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_017780.4(CHD7):c.8672A>G (p.Asn2891Ser)
  • NC_000008.11:g.60865611A>G
  • NG_007009.1:g.191832A>G
  • NM_001316690.1:c.2525A>G
  • NM_017780.4:c.8672A>GMANE SELECT
  • NP_001303619.1:p.Asn842Ser
  • NP_060250.2:p.Asn2891Ser
  • LRG_176t1:c.8672A>G
  • LRG_176:g.191832A>G
  • NC_000008.10:g.61778170A>G
  • NM_017780.2:c.8672A>G
  • NM_017780.3:c.8672A>G
  • p.Asn2891Ser
Protein change:
dbSNP: rs202039728
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001316690.1:c.2525A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017780.4:c.8672A>G - missense variant - [Sequence Ontology: SO:0001583]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000552234Invitaecriteria provided, single submitter
Uncertain significance
(Oct 19, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.

Genome Med. 2017 Feb 6;9(1):13. doi: 10.1186/s13073-017-0403-7.

PubMed [citation]

Molecular pathogenesis of congenital diaphragmatic hernia revealed by exome sequencing, developmental data, and bioinformatics.

Longoni M, High FA, Russell MK, Kashani A, Tracy AA, Coletti CM, Hila R, Shamia A, Wells J, Ackerman KG, Wilson JM, Bult CJ, Lee C, Lage K, Pober BR, Donahoe PK.

Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12450-5. doi: 10.1073/pnas.1412509111. Epub 2014 Aug 8.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000552234.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change replaces asparagine with serine at codon 2891 of the CHD7 protein (p.Asn2891Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs202039728, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with congenital diaphragmatic hernia (PMID: 25107291). ClinVar contains an entry for this variant (Variation ID: 197042). 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 serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

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