rs78359469

chr15-92996937-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001271.4(CHD2):c.3596-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,594,562 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (88 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (89 hom.)
• Consequence: CHD2 NM_001271.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.414

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 15-92996937-G-A is Benign according to our data. Variant chr15-92996937-G-A is described in ClinVar as [Benign]. Clinvar id is 257710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4	c.3596-20G>A		intron_variant		ENST00000394196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9	c.3596-20G>A		intron_variant		5	NM_001271.4	P1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2807 AN: 152172 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00488 AC: 1133 AN: 232072 Hom.: 28 AF XY: 0.00348 AC XY: 437 AN XY: 125564

Gnomad AFR exome AF: 0.0650

Gnomad AMR exome AF: 0.00247

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000578

Gnomad SAS exome AF: 0.0000763

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000139

Gnomad OTH exome AF: 0.00178

GnomAD4 exome AF: 0.00192 AC: 2773 AN: 1442272 Hom.: 89 Cov.: 31 AF XY: 0.00172 AC XY: 1230 AN XY: 717042

Gnomad4 AFR exome AF: 0.0715

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000972

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000949

Gnomad4 OTH exome AF: 0.00380

GnomAD4 genome AF: 0.0185 AC: 2819 AN: 152290 Hom.: 88 Cov.: 32 AF XY: 0.0180 AC XY: 1339 AN XY: 74462

Gnomad4 AFR AF: 0.0654

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0101 Hom.: 7

Bravo AF: 0.0207

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 12, 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	PreventionGenetics, part of Exact Sciences	-	- -

Developmental and epileptic encephalopathy 94 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	4.4
Dann	Benign	0.75
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

Other links and lift over

dbSNP: rs78359469; hg19: chr15-93540167;