rs141271290

Positions:

chr15-92941802-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001271.4(CHD2):c.693-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,609,170 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0080 ( 56 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 388 hom. )

Consequence

CHD2
NM_001271.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.128

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 15-92941802-C-T is Benign according to our data. Variant chr15-92941802-C-T is described in ClinVar as [Benign]. Clinvar id is 257715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-92941802-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD2	NM_001271.4 linkuse as main transcript	c.693-20C>T		intron_variant		ENST00000394196.9	NP_001262.3
CHD2	NM_001042572.3 linkuse as main transcript	c.693-20C>T		intron_variant			NP_001036037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9 linkuse as main transcript	c.693-20C>T		intron_variant		5	NM_001271.4	ENSP00000377747	P1	O14647-1

Frequencies

GnomAD3 genomes

AF:

0.00803

AC:

1222

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0685

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00885

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0174

AC:

4333

AN:

248624

Hom.:

281

AF XY:

0.0131

AC XY:

1763

AN XY:

134510

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00778

Gnomad SAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.000603

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00434

AC:

6330

AN:

1456954

Hom.:

388

Cov.:

AF XY:

0.00381

AC XY:

2762

AN XY:

724950

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.00156

Gnomad4 FIN exome

AF:

0.000844

Gnomad4 NFE exome

AF:

0.0000856

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.00803

AC:

1223

AN:

152216

Hom.:

Cov.:

AF XY:

0.00894

AC XY:

665

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.0685

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00887

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000944

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00400

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00664

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 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 30% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 28. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Developmental and epileptic encephalopathy 94

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.1

DANN

Benign

0.63

BranchPoint Hunter

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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