rs143043614

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001271.4(CHD2):c.1091A>G(p.Asn364Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00029 in 1,610,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N364I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

CHD2
NM_001271.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 4.16

Publications

2 publications found

Variant links:

COSMIC-nc: COSV109421015

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12121746).

BP6

Variant 15-92944453-A-G is Benign according to our data. Variant chr15-92944453-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210708.

BS2

High AC in GnomAd4 at 41 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.1091A>G	p.Asn364Ser	missense	Exon 10 of 39	NP_001262.3	O14647-1
	CHD2	NM_001042572.3		c.1091A>G	p.Asn364Ser	missense	Exon 10 of 13	NP_001036037.1	O14647-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD2	ENST00000394196.9	TSL:5 MANE Select	c.1091A>G	p.Asn364Ser	missense	Exon 10 of 39	ENSP00000377747.4	O14647-1
CHD2	ENST00000626874.2	TSL:1	c.1091A>G	p.Asn364Ser	missense	Exon 10 of 38	ENSP00000486629.1	O14647-2
CHD2	ENST00000420239.7	TSL:1	c.1091A>G	p.Asn364Ser	missense	Exon 10 of 13	ENSP00000406581.2	O14647-3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000235

AC:

AN:

251034

AF XY:

0.000199

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000292

AC:

426

AN:

1458610

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

725802

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33432

American (AMR)

AF:

0.000202

AC:

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26018

East Asian (EAS)

AF:

0.000101

AC:

AN:

39602

South Asian (SAS)

AF:

0.0000813

AC:

AN:

86060

European-Finnish (FIN)

AF:

0.0000563

AC:

AN:

53252

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.000347

AC:

385

AN:

1109680

Other (OTH)

AF:

0.000150

AC:

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000269

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41578

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000363

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CHD2-related disorder (1)

Developmental and epileptic encephalopathy 94 (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.029

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

PhyloP100

4.2

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

REVEL

Benign

0.12

Sift

Benign

0.15

Sift4G

Benign

0.17

Polyphen

0.027

Vest4

0.11

MVP

0.72

MPC

0.38

ClinPred

0.017

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.32

Mutation Taster

=88/12

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over