Genetic Variant CHD2:c.-72+12A>G (chr15-92900836-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001271.4(CHD2):c.-72+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 407,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00063 ( 0 hom. )

Consequence

CHD2
NM_001271.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.69

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 15-92900836-A-G is Benign according to our data. Variant chr15-92900836-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 384922.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 60 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4 link	c.-72+12A>G		intron_variant	Intron 1 of 38	ENST00000394196.9	NP_001262.3	O14647-1
CHD2	NM_001042572.3 link	c.-72+12A>G		intron_variant	Intron 1 of 12		NP_001036037.1	O14647-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9 link	c.-72+12A>G		intron_variant	Intron 1 of 38	5	NM_001271.4	ENSP00000377747.4		O14647-1

Frequencies

GnomAD3 genomes

AF:

0.000396

AC:

AN:

151598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000950

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000721

Gnomad OTH

AF:

0.000483

GnomAD4 exome

AF:

0.000629

AC:

161

AN:

255990

Hom.:

Cov.:

AF XY:

0.000764

AC XY:

100

AN XY:

130854

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

7158

American (AMR)

AF:

0.000796

AC:

AN:

7538

Ashkenazi Jewish (ASJ)

AF:

0.000320

AC:

AN:

9386

East Asian (EAS)

AF:

0.00

AC:

AN:

22608

South Asian (SAS)

AF:

0.00

AC:

AN:

5884

European-Finnish (FIN)

AF:

0.000439

AC:

AN:

20504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1314

European-Non Finnish (NFE)

AF:

0.000850

AC:

140

AN:

164634

Other (OTH)

AF:

0.000177

AC:

AN:

16964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000395

AC:

AN:

151716

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41322

American (AMR)

AF:

0.000395

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.0000950

AC:

AN:

10522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000721

AC:

AN:

67944

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000318

Hom.:

Bravo

AF:

0.000461

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 03, 2018

GeneDx

Significance:Likely 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

-0.51

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.7

PromoterAI

-0.018

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

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.

15-92900836-A-G

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