rs34315566

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.4527C>T(p.Ile1509Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,614,118 control chromosomes in the GnomAD database, including 2,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 239 hom., cov: 33)

Exomes 𝑓: 0.051 ( 2473 hom. )

Consequence

CHD2
NM_001271.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.60

Publications

5 publications found

Variant links:

COSMIC-nc: COSV104431434

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=-0.31).

BP6

Variant 15-93009258-C-T is Benign according to our data. Variant chr15-93009258-C-T is described in ClinVar as Benign. ClinVar VariationId is 257711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4 link	c.4527C>T	p.Ile1509Ile	synonymous_variant	Exon 35 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.4527C>T	p.Ile1509Ile	synonymous_variant	Exon 35 of 39	5	NM_001271.4	ENSP00000377747.4		O14647-1

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6311

AN:

152156

Hom.:

239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00902

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0588

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0441

AC:

11083

AN:

251356

AF XY:

0.0437

show subpopulations

Gnomad AFR exome

AF:

0.00745

Gnomad AMR exome

AF:

0.00960

Gnomad ASJ exome

AF:

0.00724

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.0608

Gnomad OTH exome

AF:

0.0396

GnomAD4 exome

AF:

0.0509

AC:

74370

AN:

1461844

Hom.:

2473

Cov.:

AF XY:

0.0499

AC XY:

36282

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00723

AC:

242

AN:

33478

American (AMR)

AF:

0.00991

AC:

443

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00781

AC:

204

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00974

AC:

840

AN:

86250

European-Finnish (FIN)

AF:

0.148

AC:

7912

AN:

53420

Middle Eastern (MID)

AF:

0.00745

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0559

AC:

62160

AN:

1111982

Other (OTH)

AF:

0.0418

AC:

2524

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3886

7772

11659

15545

19431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2232

4464

6696

8928

11160

<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:

0.0414

AC:

6309

AN:

152274

Hom.:

239

Cov.:

AF XY:

0.0435

AC XY:

3237

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00900

AC:

374

AN:

41566

American (AMR)

AF:

0.0115

AC:

176

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00725

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.153

AC:

1627

AN:

10600

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0588

AC:

3998

AN:

68008

Other (OTH)

AF:

0.0279

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

301

602

904

1205

1506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0473

Hom.:

138

Bravo

AF:

0.0291

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 18, 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 09, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 26, 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. -

Developmental and epileptic encephalopathy 94

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

1.1

(source)

DANN

Benign

0.89

PhyloP100

-1.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

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