rs144294063

chr15-92946054-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001271.4(CHD2):c.1215G>A(p.Pro405=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,584,522 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 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: CHD2 NM_001271.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 15-92946054-G-A is Benign according to our data. Variant chr15-92946054-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474373.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-92946054-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BS2: High AC in GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHD2	NM_001271.4	c.1215G>A	p.Pro405=	synonymous_variant	12/39	ENST00000394196.9
CHD2	NM_001042572.3	c.1215G>A	p.Pro405=	synonymous_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHD2	ENST00000394196.9	c.1215G>A	p.Pro405=	synonymous_variant	12/39	5	NM_001271.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000109 AC: 26 AN: 239320 Hom.: 0 AF XY: 0.000108 AC XY: 14 AN XY: 129714

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000972

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000676

Gnomad SAS exome AF: 0.000282

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.0000237 AC: 34 AN: 1432342 Hom.: 0 Cov.: 31 AF XY: 0.0000282 AC XY: 20 AN XY: 710430

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000739

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000254

Gnomad4 SAS exome AF: 0.000111

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000100

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74408

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy 94 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	3.7
Dann	Benign	0.69
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs144294063; hg19: chr15-93489284; COSMIC: COSV59119348; COSMIC: COSV59119348;