NM_001271.4(CHD2):c.2699G>A (p.Arg900Gln) AND Developmental and epileptic encephalopathy 94

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 19, 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:: RCV000679946.10

Allele description [Variation Report for NM_001271.4(CHD2):c.2699G>A (p.Arg900Gln)]

NM_001271.4(CHD2):c.2699G>A (p.Arg900Gln)

Gene:

CHD2:chromodomain helicase DNA binding protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_001271.4(CHD2):c.2699G>A (p.Arg900Gln)

HGVS:

NC_000015.10:g.92978355G>A
NG_012826.2:g.83035G>A
NM_001271.4:c.2699G>AMANE SELECT
NP_001262.3:p.Arg900Gln
LRG_1425t1:c.2699G>A
LRG_1425:g.83035G>A
LRG_1425p1:p.Arg900Gln
NC_000015.9:g.93521585G>A
NG_012826.1:g.83035G>A
NM_001271.3:c.2699G>A

Protein change:

R900Q

Links:

dbSNP: rs1567149946

NCBI 1000 Genomes Browser:

rs1567149946

Molecular consequence:

NM_001271.4:c.2699G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy 94 (DEE94)
Synonyms:: Epileptic encephalopathy, childhood-onset
Identifiers:: MONDO: MONDO:0014150; MedGen: C3809278; Orphanet: 1942; Orphanet: 2382; OMIM: 615369

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Chain z, RPB12
Chain z, RPB12
gi|2033713687|pdb|7EGB|z

Protein
Chain i, Transcription initiation factor TFIID subunit 9
Chain i, Transcription initiation factor TFIID subunit 9
gi|2033713671|pdb|7EGB|i

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000807380	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 25326635
SCV001575741	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 19, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25326635, 30525188, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000807380

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

unknown

clinical testing

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

SCV001575741

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 19, 2022)

germline

clinical testing

PubMed (3)
[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	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

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

Molecular findings among patients referred for clinical whole-exome sequencing.

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, et al.

JAMA. 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601.

PubMed [citation]

PMID:: 25326635
PMCID:: PMC4326249

See all PubMed Citations (4)

Details of each submission

From Baylor Genetics, SCV000807380.3

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

#	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

From Invitae, SCV001575741.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense change has been observed in individual(s) with clinical features of CHD2-related conditions (PMID: 25326635, 30525188). 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 replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 900 of the CHD2 protein (p.Arg900Gln). ClinVar contains an entry for this variant (Variation ID: 560973). For these reasons, this variant has been classified as Pathogenic. 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 CHD2 protein function.

#	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: Aug 25, 2024

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