rs12906163

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001271.4(CHD2):c.5416A>C(p.Arg1806=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,613,926 control chromosomes in the GnomAD database, including 108,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7212 hom., cov: 32)

Exomes 𝑓: 0.36 ( 100886 hom. )

Consequence

CHD2
NM_001271.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.978

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 15-93024634-A-C is Benign according to our data. Variant chr15-93024634-A-C is described in ClinVar as [Benign]. Clinvar id is 257713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.978 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4 linkuse as main transcript	c.5416A>C	p.Arg1806=	synonymous_variant	39/39	ENST00000394196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9 linkuse as main transcript	c.5416A>C	p.Arg1806=	synonymous_variant	39/39	5	NM_001271.4	P1	O14647-1
CHD2	ENST00000625662.3 linkuse as main transcript	c.*1587A>C		3_prime_UTR_variant, NMD_transcript_variant	35/35	5
CHD2	ENST00000627460.1 linkuse as main transcript	c.*548A>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42904

AN:

152056

Hom.:

7210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.0728

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.295

AC:

73504

AN:

249530

Hom.:

12678

AF XY:

0.305

AC XY:

41337

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.0719

Gnomad SAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.361

AC:

527915

AN:

1461752

Hom.:

100886

Cov.:

AF XY:

0.360

AC XY:

261745

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.434

Gnomad4 EAS exome

AF:

0.0645

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.346

GnomAD4 genome

AF:

0.282

AC:

42922

AN:

152174

Hom.:

7212

Cov.:

AF XY:

0.274

AC XY:

20396

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.435

Gnomad4 EAS

AF:

0.0728

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.317

Alfa

AF:

0.352

Hom.:

8407

Bravo

AF:

0.278

Asia WGS

AF:

0.184

AC:

637

AN:

3478

EpiCase

AF:

0.418

EpiControl

AF:

0.415

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 07, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 43. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Developmental and epileptic encephalopathy 94

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.9

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over