rs12906163

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

-21

BP4_StrongBP6_Very_StrongBP7BA1

The NM_001271.4(CHD2):c.5416A>C(p.Arg1806Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,613,926 control chromosomes in the GnomAD database, including 108,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7212 hom., cov: 32)

Exomes 𝑓: 0.36 ( 100886 hom. )

Consequence

CHD2
NM_001271.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.978

Publications

20 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=-0.65).

BP6

Variant 15-93024634-A-C is Benign according to our data. Variant chr15-93024634-A-C is described in ClinVar as [Benign]. Clinvar id is 257713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.978 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4 link	c.5416A>C	p.Arg1806Arg	synonymous_variant	Exon 39 of 39	ENST00000394196.9	NP_001262.3	O14647-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9 link	c.5416A>C	p.Arg1806Arg	synonymous_variant	Exon 39 of 39	5	NM_001271.4	ENSP00000377747.4		O14647-1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42904

AN:

152056

Hom.:

7210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.0728

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.322

GnomAD2 exomes

AF:

0.295

AC:

73504

AN:

249530

AF XY:

0.305

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.0719

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.361

AC:

527915

AN:

1461752

Hom.:

100886

Cov.:

AF XY:

0.360

AC XY:

261745

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.129

AC:

4312

AN:

33478

American (AMR)

AF:

0.192

AC:

8583

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

11345

AN:

26136

East Asian (EAS)

AF:

0.0645

AC:

2560

AN:

39700

South Asian (SAS)

AF:

0.275

AC:

23749

AN:

86256

European-Finnish (FIN)

AF:

0.236

AC:

12622

AN:

53416

Middle Eastern (MID)

AF:

0.425

AC:

2452

AN:

5768

European-Non Finnish (NFE)

AF:

0.397

AC:

441371

AN:

1111882

Other (OTH)

AF:

0.346

AC:

20921

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

18574

37149

55723

74298

92872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13410

26820

40230

53640

67050

<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:

0.282

AC:

42922

AN:

152174

Hom.:

7212

Cov.:

AF XY:

0.274

AC XY:

20396

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.136

AC:

5642

AN:

41522

American (AMR)

AF:

0.263

AC:

4028

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.435

AC:

1508

AN:

3468

East Asian (EAS)

AF:

0.0728

AC:

378

AN:

5192

South Asian (SAS)

AF:

0.252

AC:

1212

AN:

4814

European-Finnish (FIN)

AF:

0.227

AC:

2409

AN:

10590

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26526

AN:

67978

Other (OTH)

AF:

0.317

AC:

670

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1510

3021

4531

6042

7552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.330

Hom.:

11713

Bravo

AF:

0.278

Asia WGS

AF:

0.184

AC:

637

AN:

3478

EpiCase

AF:

0.418

EpiControl

AF:

0.415

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 07, 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

- -

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 46% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 43. Only high quality variants are reported. -

not provided

Benign:2

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Developmental and epileptic encephalopathy 94

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.65

CADD

Benign

7.9

(source)

DANN

Benign

0.68

PhyloP100

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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