20-41405177-G-C

Position:

• chr20-41405177-G-C

Variant summary

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

The ENST00000373233.8(CHD6):​c.7564C>G​(p.Leu2522Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHD6 ENST00000373233.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

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]

ACMG classification

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	c.7564C>G	p.Leu2522Val	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	c.7564C>G	p.Leu2522Val	missense_variant	37/37	1	NM_032221.5	ENSP00000362330	P1
CHD6	ENST00000480022.1	n.2175C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.7564C>G (p.L2522V) alteration is located in exon 37 (coding exon 36) of the CHD6 gene. This alteration results from a C to G substitution at nucleotide position 7564, causing the leucine (L) at amino acid position 2522 to be replaced by a valine (V). 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	Benign	0.28
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	2.9	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.23		Gain of catalytic residue at L2522 (P = 0.1298);
MVP		0.84
MPC		0.66
ClinPred		0.93	D
GERP RS		4.6
Varity_R		0.21
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-40033817; COSMIC: COSV64691026;