chr15-92992967-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001271.4(CHD2):c.3564C>T(p.Tyr1188Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,568 control chromosomes in the GnomAD database, including 56,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4435 hom., cov: 33)

Exomes 𝑓: 0.26 ( 51711 hom. )

Consequence

CHD2
NM_001271.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0580

Publications

19 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 15-92992967-C-T is Benign according to our data. Variant chr15-92992967-C-T is described in ClinVar as Benign. ClinVar VariationId is 257709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.058 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4 link	c.3564C>T	p.Tyr1188Tyr	synonymous_variant	Exon 28 of 39	ENST00000394196.9	NP_001262.3	O14647-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHD2	ENST00000394196.9 link	c.3564C>T	p.Tyr1188Tyr	synonymous_variant	Exon 28 of 39	5	NM_001271.4	ENSP00000377747.4	O14647-1
CHD2	ENST00000637789.1 link	n.*139C>T		non_coding_transcript_exon_variant	Exon 5 of 9	5		ENSP00000489767.1	A0A1B0GTM9
CHD2	ENST00000637789.1 link	n.*139C>T		3_prime_UTR_variant	Exon 5 of 9	5		ENSP00000489767.1	A0A1B0GTM9

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35359

AN:

152008

Hom.:

4433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.264

GnomAD2 exomes

AF:

0.225

AC:

56331

AN:

250532

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.186

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.261

AC:

381880

AN:

1461442

Hom.:

51711

Cov.:

AF XY:

0.260

AC XY:

189057

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.193

AC:

6453

AN:

33470

American (AMR)

AF:

0.170

AC:

7598

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7376

AN:

26130

East Asian (EAS)

AF:

0.151

AC:

6003

AN:

39696

South Asian (SAS)

AF:

0.210

AC:

18079

AN:

86242

European-Finnish (FIN)

AF:

0.155

AC:

8283

AN:

53384

Middle Eastern (MID)

AF:

0.357

AC:

1997

AN:

5598

European-Non Finnish (NFE)

AF:

0.279

AC:

310745

AN:

1111838

Other (OTH)

AF:

0.254

AC:

15346

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

14499

28998

43497

57996

72495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10214

20428

30642

40856

51070

<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:

0.233

AC:

35380

AN:

152126

Hom.:

4435

Cov.:

AF XY:

0.229

AC XY:

17040

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.188

AC:

7811

AN:

41504

American (AMR)

AF:

0.229

AC:

3494

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

970

AN:

3466

East Asian (EAS)

AF:

0.135

AC:

702

AN:

5182

South Asian (SAS)

AF:

0.211

AC:

1018

AN:

4814

European-Finnish (FIN)

AF:

0.139

AC:

1473

AN:

10590

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18868

AN:

67982

Other (OTH)

AF:

0.264

AC:

556

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1384

2767

4151

5534

6918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.267

Hom.:

25319

Bravo

AF:

0.238

Asia WGS

AF:

0.186

AC:

646

AN:

3478

EpiCase

AF:

0.305

EpiControl

AF:

0.305

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 42% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 39. Only high quality variants are reported. -

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

- -

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

-0.39

CADD

Benign

6.7

(source)

DANN

Benign

0.89

PhyloP100

0.058

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

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