NM_001271.4:c.63-6180C>G

Variant names:

• chr15-92918141-C-G
• rs1406714
• NM_001271.4:c.63-6180C>G

Variant summary

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

The NM_001271.4(CHD2):​c.63-6180C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,036 control chromosomes in the GnomAD database, including 25,195 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 0.57 (25195 hom., cov: 32)
• Consequence: CHD2 NM_001271.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD2	NM_001271.4	c.63-6180C>G		intron_variant	Intron 2 of 38	ENST00000394196.9	NP_001262.3
CHD2	NM_001042572.3	c.63-6180C>G		intron_variant	Intron 2 of 12		NP_001036037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD2	ENST00000394196.9	c.63-6180C>G		intron_variant	Intron 2 of 38	5	NM_001271.4	ENSP00000377747.4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86344 AN: 151918 Hom.: 25164 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.568 AC: 86425 AN: 152036 Hom.: 25195 Cov.: 32 AF XY: 0.576 AC XY: 42809 AN XY: 74328

African (AFR) AF: 0.475 AC: 19672 AN: 41434

American (AMR) AF: 0.661 AC: 10110 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4435 AN: 5174

South Asian (SAS) AF: 0.733 AC: 3535 AN: 4824

European-Finnish (FIN) AF: 0.619 AC: 6532 AN: 10558

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38156 AN: 67982

Other (OTH) AF: 0.570 AC: 1199 AN: 2104

Alfa AF: 0.434 Hom.: 1198

Bravo AF: 0.568

Asia WGS AF: 0.767 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.43
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1406714; hg19: chr15-93461371;