15-92978374-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001271.4(CHD2):c.2718A>G(p.Gln906Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,613,670 control chromosomes in the GnomAD database, including 562,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 46139 hom., cov: 31)

Exomes 𝑓: 0.84 ( 516624 hom. )

Consequence

CHD2
NM_001271.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.64

Publications

21 publications found

Variant links:

Genes affected

CHD2 (HGNC:1917): (chromodomain helicase DNA binding protein 2) The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CHD2 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy 94
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Lennox-Gastaut syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
myoclonic-astatic epilepsy
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

CHD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 15-92978374-A-G is Benign according to our data. Variant chr15-92978374-A-G is described in ClinVar as Benign. ClinVar VariationId is 257708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4 link	c.2718A>G	p.Gln906Gln	synonymous_variant	Exon 21 of 39	ENST00000394196.9	NP_001262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9 link	c.2718A>G	p.Gln906Gln	synonymous_variant	Exon 21 of 39	5	NM_001271.4	ENSP00000377747.4

Frequencies

GnomAD3 genomes

AF:

0.767

AC:

116496

AN:

151902

Hom.:

46101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.935

Gnomad AMR

AF:

0.881

Gnomad ASJ

AF:

0.908

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.908

Gnomad FIN

AF:

0.754

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.816

GnomAD2 exomes

AF:

0.844

AC:

210204

AN:

248986

AF XY:

0.850

show subpopulations

Gnomad AFR exome

AF:

0.559

Gnomad AMR exome

AF:

0.918

Gnomad ASJ exome

AF:

0.906

Gnomad EAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.765

Gnomad NFE exome

AF:

0.831

Gnomad OTH exome

AF:

0.858

GnomAD4 exome

AF:

0.839

AC:

1225767

AN:

1461650

Hom.:

516624

Cov.:

AF XY:

0.841

AC XY:

611422

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.565

AC:

18900

AN:

33472

American (AMR)

AF:

0.912

AC:

40800

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

23700

AN:

26136

East Asian (EAS)

AF:

0.998

AC:

39633

AN:

39696

South Asian (SAS)

AF:

0.899

AC:

77554

AN:

86256

European-Finnish (FIN)

AF:

0.759

AC:

40562

AN:

53412

Middle Eastern (MID)

AF:

0.919

AC:

5303

AN:

5768

European-Non Finnish (NFE)

AF:

0.835

AC:

928731

AN:

1111804

Other (OTH)

AF:

0.838

AC:

50584

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

9960

19919

29879

39838

49798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21068

42136

63204

84272

105340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.767

AC:

116584

AN:

152020

Hom.:

46139

Cov.:

AF XY:

0.772

AC XY:

57365

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.559

AC:

23169

AN:

41428

American (AMR)

AF:

0.881

AC:

13454

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.908

AC:

3152

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5165

AN:

5176

South Asian (SAS)

AF:

0.908

AC:

4381

AN:

4824

European-Finnish (FIN)

AF:

0.754

AC:

7939

AN:

10536

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.831

AC:

56481

AN:

67996

Other (OTH)

AF:

0.818

AC:

1725

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1183

2366

3548

4731

5914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.810

Hom.:

44642

Bravo

AF:

0.769

Asia WGS

AF:

0.931

AC:

3238

AN:

3478

EpiCase

AF:

0.851

EpiControl

AF:

0.855

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jan 05, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 90. Only high quality variants are reported.

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Developmental and epileptic encephalopathy 94

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.0

(source)

DANN

Benign

0.65

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over