rs767309501

Variant names:

• chr15-92972421-A-C
• rs767309501
• NM_001271.4:c.2505+4A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-92972421-A-C
• chr15-92972421-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271.4(CHD2):​c.2505+4A>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000699 in 1,430,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CHD2 NM_001271.4 splice_region, intron
• Scores: Splicing: ADA: 0.1219
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4	c.2505+4A>C		splice_region_variant, intron_variant	Intron 19 of 38	ENST00000394196.9	NP_001262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.2505+4A>C		splice_region_variant, intron_variant	Intron 19 of 38	5	NM_001271.4	ENSP00000377747.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000446 AC: 1 AN: 224008 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430836 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710890

African (AFR) AF: 0.00 AC: 0 AN: 31452

American (AMR) AF: 0.00 AC: 0 AN: 37194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25040

East Asian (EAS) AF: 0.00 AC: 0 AN: 38350

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099170

Other (OTH) AF: 0.00 AC: 0 AN: 59028

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Benign	0.91
PhyloP100		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.49

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

Other links and lift over

dbSNP: rs767309501; hg19: chr15-93515651;