15-93014724-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001271.4(CHD2):c.4721G>C(p.Gly1574Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0257 in 1,613,986 control chromosomes in the GnomAD database, including 635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1574V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.019 ( 38 hom., cov: 32)

Exomes 𝑓: 0.026 ( 597 hom. )

Consequence

CHD2
NM_001271.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.86

Publications

10 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: Labcorp Genetics (formerly Invitae), G2P
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

new If you want to explore the variant's impact on the transcript NM_001271.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034458637).

BP6

Variant 15-93014724-G-C is Benign according to our data. Variant chr15-93014724-G-C is described in ClinVar as Benign. ClinVar VariationId is 257712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0194 (2954/152174) while in subpopulation NFE AF = 0.0301 (2044/67988). AF 95% confidence interval is 0.029. There are 38 homozygotes in GnomAd4. There are 1363 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2954 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD2	NM_001271.4	MANE Select	c.4721G>C	p.Gly1574Ala	missense	Exon 37 of 39	NP_001262.3	O14647-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD2	ENST00000394196.9	TSL:5 MANE Select	c.4721G>C	p.Gly1574Ala	missense	Exon 37 of 39	ENSP00000377747.4	O14647-1
CHD2	ENST00000626874.2	TSL:1	c.4721G>C	p.Gly1574Ala	missense	Exon 37 of 38	ENSP00000486629.1	O14647-2
CHD2	ENST00000625662.3	TSL:5	n.*892G>C		non_coding_transcript_exon	Exon 33 of 35	ENSP00000486007.2	A0A0D9SEU0

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2954

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00529

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0206

AC:

5173

AN:

251390

AF XY:

0.0208

show subpopulations

Gnomad AFR exome

AF:

0.00468

Gnomad AMR exome

AF:

0.00758

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.0313

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.0263

AC:

38452

AN:

1461812

Hom.:

597

Cov.:

AF XY:

0.0257

AC XY:

18694

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00376

AC:

126

AN:

33480

American (AMR)

AF:

0.00816

AC:

365

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0143

AC:

374

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00421

AC:

363

AN:

86250

European-Finnish (FIN)

AF:

0.0390

AC:

2082

AN:

53418

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0304

AC:

33853

AN:

1111946

Other (OTH)

AF:

0.0211

AC:

1276

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1855

3710

5566

7421

9276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1226

2452

3678

4904

6130

<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:

0.0194

AC:

2954

AN:

152174

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1363

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00527

AC:

219

AN:

41520

American (AMR)

AF:

0.0103

AC:

157

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00353

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0403

AC:

427

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0301

AC:

2044

AN:

67988

Other (OTH)

AF:

0.0133

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

145

289

434

578

723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0217

Hom.:

Bravo

AF:

0.0164

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0268

EpiControl

AF:

0.0265

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Developmental and epileptic encephalopathy 94 (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.068

Eigen

Benign

-0.14

Eigen_PC

Benign

0.078

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.1

PhyloP100

6.9

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.65

REVEL

Uncertain

0.36

Sift

Benign

0.89

Sift4G

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.054

gMVP

0.24

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over