rs78359469

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001271.4(CHD2):c.3596-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,594,562 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 88 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 89 hom. )

Consequence

CHD2
NM_001271.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.414

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 15-92996937-G-A is Benign according to our data. Variant chr15-92996937-G-A is described in ClinVar as Benign. ClinVar VariationId is 257710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4 link	c.3596-20G>A		intron_variant	Intron 28 of 38	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.3596-20G>A		intron_variant	Intron 28 of 38	5	NM_001271.4	ENSP00000377747.4		O14647-1
CHD2	ENST00000637789.1 link	n.*171-20G>A		intron_variant	Intron 5 of 8	5		ENSP00000489767.1		A0A1B0GTM9

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2807

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00488

AC:

1133

AN:

232072

AF XY:

0.00348

show subpopulations

Gnomad AFR exome

AF:

0.0650

Gnomad AMR exome

AF:

0.00247

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000578

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000139

Gnomad OTH exome

AF:

0.00178

GnomAD4 exome

AF:

0.00192

AC:

2773

AN:

1442272

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1230

AN XY:

717042

show subpopulations

African (AFR)

AF:

0.0715

AC:

2293

AN:

32092

American (AMR)

AF:

0.00297

AC:

116

AN:

39094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25020

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.0000972

AC:

AN:

82274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52922

Middle Eastern (MID)

AF:

0.00444

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.0000949

AC:

105

AN:

1106114

Other (OTH)

AF:

0.00380

AC:

226

AN:

59532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

112

223

335

446

558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0185

AC:

2819

AN:

152290

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1339

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0654

AC:

2716

AN:

41542

American (AMR)

AF:

0.00464

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

260

391

521

651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0103

Hom.:

Bravo

AF:

0.0207

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 12, 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:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Developmental and epileptic encephalopathy 94

Benign:1

Feb 03, 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

-0.68

CADD

Benign

4.4

(source)

DANN

Benign

0.75

PhyloP100

-0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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