dbSNP rs7179432: CHD2:c.*1417T>C (chr15-93021742-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000626874.2(CHD2):c.*1417T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,016 control chromosomes in the GnomAD database, including 16,681 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16680 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

CHD2
ENST00000626874.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.295

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4 link	c.5153+1484T>C		intron_variant	Intron 38 of 38	ENST00000394196.9	NP_001262.3	O14647-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHD2	ENST00000626874.2 link	c.*1417T>C	3_prime_UTR_variant	Exon 38 of 38	1		ENSP00000486629.1	O14647-2
CHD2	ENST00000394196.9 link	c.5153+1484T>C	intron_variant	Intron 38 of 38	5	NM_001271.4	ENSP00000377747.4	O14647-1
CHD2	ENST00000625662.3 link	n.*1324+1484T>C	intron_variant	Intron 34 of 34	5		ENSP00000486007.2	A0A0D9SEU0
CHD2	ENST00000627460.1 link	n.*285+1484T>C	intron_variant	Intron 4 of 4	5		ENSP00000485982.1	A0A0D9SET4

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68558

AN:

151896

Hom.:

16666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.896

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

Exome Hom

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

GnomAD4 genome

AF:

0.451

AC:

68594

AN:

152014

Hom.:

16680

Cov.:

AF XY:

0.462

AC XY:

34345

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.321

AC:

13320

AN:

41448

American (AMR)

AF:

0.512

AC:

7823

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1320

AN:

3464

East Asian (EAS)

AF:

0.896

AC:

4647

AN:

5188

South Asian (SAS)

AF:

0.585

AC:

2816

AN:

4814

European-Finnish (FIN)

AF:

0.602

AC:

6338

AN:

10536

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.455

AC:

30927

AN:

67966

Other (OTH)

AF:

0.448

AC:

947

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1818

3636

5455

7273

9091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

632

1264

1896

2528

3160

<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:

0.443

Hom.:

33013

Bravo

AF:

0.437

Asia WGS

AF:

0.700

AC:

2434

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

(source)

DANN

Benign

0.72

PhyloP100

-0.29

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

Computational scores

Splicing

Publications

Other links and lift over