NM_017780.4(CHD7):c.6070C>T (p.Arg2024Ter) AND CHARGE syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 14, 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:: RCV000659301.8

Allele description [Variation Report for NM_017780.4(CHD7):c.6070C>T (p.Arg2024Ter)]

NM_017780.4(CHD7):c.6070C>T (p.Arg2024Ter)

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.6070C>T (p.Arg2024Ter)

HGVS:

NC_000008.11:g.60852673C>T
NG_007009.1:g.178894C>T
NM_001316690.1:c.1717-9556C>T
NM_017780.4:c.6070C>TMANE SELECT
NP_060250.2:p.Arg2024Ter
LRG_176t1:c.6070C>T
LRG_176:g.178894C>T
NC_000008.10:g.61765232C>T
NM_017780.2:c.6070C>T
NM_017780.3:c.6070C>T

Protein change:

R2024*

Links:

dbSNP: rs1360515765

NCBI 1000 Genomes Browser:

rs1360515765

Molecular consequence:

NM_001316690.1:c.1717-9556C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_017780.4:c.6070C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Clear Turn Off Turn On

cytochrome oxidase subunit I, partial (mitochondrion) [Moina micrura]
cytochrome oxidase subunit I, partial (mitochondrion) [Moina micrura]
gi|1009658480|gb|AMR72706.1|

Protein

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
SCV000781109	Center for Human Genetics, Inc, Center for Human Genetics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001582550	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 14, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15300250, 26538304, 22461308, 25077900, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000781109

Center for Human Genetics, Inc, Center for Human Genetics, Inc

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 1, 2016)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001582550

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 14, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.

Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG.

Nat Genet. 2004 Sep;36(9):955-7. Epub 2004 Aug 8.

PubMed [citation]

PMID:: 15300250

See all PubMed Citations (6)

Details of each submission

From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000781109.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001582550.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

ClinVar contains an entry for this variant (Variation ID: 547195). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This premature translational stop signal has been observed in individual(s) with CHARGE syndrome (PMID: 15300250, 26538304). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg2024*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900).

#	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