rs1406712

Variant names:

• chr15-92974463-T-C
• rs1406712
• NM_001271.4:c.2506-416T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001271.4(CHD2):​c.2506-416T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,296 control chromosomes in the GnomAD database, including 491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.078 (491 hom., cov: 32)
• Consequence: CHD2 NM_001271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD2	NM_001271.4	MANE Select	c.2506-416T>C		intron	N/A	NP_001262.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD2	ENST00000394196.9	TSL:5 MANE Select	c.2506-416T>C		intron	N/A	ENSP00000377747.4
	CHD2	ENST00000626874.2	TSL:1	c.2506-416T>C		intron	N/A	ENSP00000486629.1
	CHD2	ENST00000625463.1	TSL:1	c.46-416T>C		intron	N/A	ENSP00000486391.1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11883 AN: 152178 Hom.: 491 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00461

Gnomad SAS AF: 0.0905

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.0974

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0780 AC: 11885 AN: 152296 Hom.: 491 Cov.: 32 AF XY: 0.0765 AC XY: 5695 AN XY: 74466

African (AFR) AF: 0.0799 AC: 3319 AN: 41554

American (AMR) AF: 0.0677 AC: 1036 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3470

East Asian (EAS) AF: 0.00462 AC: 24 AN: 5190

South Asian (SAS) AF: 0.0910 AC: 438 AN: 4814

European-Finnish (FIN) AF: 0.0453 AC: 481 AN: 10624

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0865 AC: 5884 AN: 68020

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0779 Hom.: 95

Bravo AF: 0.0796

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.66
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1406712; hg19: chr15-93517693;