rs190159225

chr15-92972255-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001271.4(CHD2):c.2353-10A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,603,684 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: CHD2 NM_001271.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002751
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.962

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-92972255-A-G is Benign according to our data. Variant chr15-92972255-A-G is described in ClinVar as [Benign]. Clinvar id is 384397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-92972255-A-G is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 244 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4	c.2353-10A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000394196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9	c.2353-10A>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001271.4	P1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152236 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00171 AC: 415 AN: 242288 Hom.: 1 AF XY: 0.00189 AC XY: 248 AN XY: 131430

Gnomad AFR exome AF: 0.000251

Gnomad AMR exome AF: 0.000776

Gnomad ASJ exome AF: 0.00329

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00187

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.00169

GnomAD4 exome AF: 0.00172 AC: 2496 AN: 1451330 Hom.: 6 Cov.: 30 AF XY: 0.00174 AC XY: 1255 AN XY: 722358

Gnomad4 AFR exome AF: 0.000215

Gnomad4 AMR exome AF: 0.000903

Gnomad4 ASJ exome AF: 0.00236

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00184

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00186

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.00160 AC: 244 AN: 152354 Hom.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132 AN XY: 74504

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00257

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00219 Hom.: 2

Bravo AF: 0.00173

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 09, 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. -

Developmental and epileptic encephalopathy 94 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.44
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.0020

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

Publications

LitVar

Other links and lift over

dbSNP: rs190159225; hg19: chr15-93515485;