Variant 20-41405415-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000373233.8(CHD6):c.7326G>T(p.Arg2442Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2442T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CHD6
ENST00000373233.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.309

Variant links:

Genes affected

CHD6 (HGNC:19057): (chromodomain helicase DNA binding protein 6) This gene encodes a member of the SNF2/RAD54 helicase protein family. The encoded protein contains two chromodomains, a helicase domain, and an ATPase domain. Several multi-subunit protein complexes remodel chromatin to allow patterns of cell type-specific gene expression, and the encoded protein is thought to be a core member of one or more of these chromatin remodeling complexes. The encoded protein may function as a transcriptional repressor and is involved in the cellular repression of influenza virus replication. [provided by RefSeq, Jul 2013]

CHD6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD6	NM_032221.5 linkuse as main transcript	c.7326G>T	p.Arg2442Ser	missense_variant	37/37	ENST00000373233.8	NP_115597.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD6	ENST00000373233.8 linkuse as main transcript	c.7326G>T	p.Arg2442Ser	missense_variant	37/37	1	NM_032221.5	ENSP00000362330	P1	Q8TD26-1
CHD6	ENST00000480022.1 linkuse as main transcript	n.1937G>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460180

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.7326G>T (p.R2442S) alteration is located in exon 37 (coding exon 36) of the CHD6 gene. This alteration results from a G to T substitution at nucleotide position 7326, causing the arginine (R) at amino acid position 2442 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.45

MetaRNN

Uncertain

0.58

MetaSVM

Uncertain

0.71

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.9

REVEL

Pathogenic

0.75

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.48

MutPred

0.51

Gain of phosphorylation at R2442 (P = 6e-04);

MVP

0.86

MPC

0.69

ClinPred

0.98

GERP RS

1.3

Varity_R

0.61

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over