15-92967373-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.2049A>G(p.Glu683Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 1,611,470 control chromosomes in the GnomAD database, including 568,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 47698 hom., cov: 29)

Exomes 𝑓: 0.84 ( 520823 hom. )

Consequence

CHD2
NM_001271.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.420

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=-0.55).

BP6

Variant 15-92967373-A-G is Benign according to our data. Variant chr15-92967373-A-G is described in ClinVar as Benign. ClinVar VariationId is 257706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.42 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.2049A>G	p.Glu683Glu	synonymous_variant	Exon 17 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.2049A>G	p.Glu683Glu	synonymous_variant	Exon 17 of 39	5	NM_001271.4	ENSP00000377747.4		O14647-1

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

118976

AN:

151760

Hom.:

47659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.935

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.908

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.908

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.825

GnomAD2 exomes

AF:

0.850

AC:

212954

AN:

250602

AF XY:

0.854

show subpopulations

Gnomad AFR exome

AF:

0.611

Gnomad AMR exome

AF:

0.922

Gnomad ASJ exome

AF:

0.906

Gnomad EAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.766

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.843

AC:

1230399

AN:

1459588

Hom.:

520823

Cov.:

AF XY:

0.845

AC XY:

613480

AN XY:

726182

show subpopulations

African (AFR)

AF:

0.619

AC:

20652

AN:

33386

American (AMR)

AF:

0.916

AC:

40908

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.907

AC:

23659

AN:

26082

East Asian (EAS)

AF:

0.998

AC:

39585

AN:

39648

South Asian (SAS)

AF:

0.900

AC:

77495

AN:

86142

European-Finnish (FIN)

AF:

0.760

AC:

40575

AN:

53386

Middle Eastern (MID)

AF:

0.922

AC:

5305

AN:

5756

European-Non Finnish (NFE)

AF:

0.839

AC:

931382

AN:

1110256

Other (OTH)

AF:

0.843

AC:

50838

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

8366

16732

25097

33463

41829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21070

42140

63210

84280

105350

<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:

0.784

AC:

119069

AN:

151882

Hom.:

47698

Cov.:

AF XY:

0.789

AC XY:

58555

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.613

AC:

25354

AN:

41346

American (AMR)

AF:

0.887

AC:

13520

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.908

AC:

3150

AN:

3468

East Asian (EAS)

AF:

0.998

AC:

5158

AN:

5170

South Asian (SAS)

AF:

0.909

AC:

4371

AN:

4810

European-Finnish (FIN)

AF:

0.755

AC:

7976

AN:

10568

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.834

AC:

56681

AN:

67956

Other (OTH)

AF:

0.826

AC:

1741

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1210

2420

3631

4841

6051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.823

Hom.:

149628

Bravo

AF:

0.788

Asia WGS

AF:

0.934

AC:

3249

AN:

3478

EpiCase

AF:

0.854

EpiControl

AF:

0.857

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 98% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 91. Only high quality variants are reported. -

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

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

-0.55

CADD

Benign

7.4

(source)

DANN

Benign

0.63

PhyloP100

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=93/7

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