NM_017780.4:c.6079C>G

Variant names:

• chr8-60852682-C-G
• rs886040995
• NM_017780.4:c.6079C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017780.4(CHD7):​c.6079C>G​(p.Arg2027Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2027Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD7 NM_017780.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• Publications: 0 publications found

Genes affected

CHD7 (HGNC:20626): (chromodomain helicase DNA binding protein 7) This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

CHD7 Gene-Disease associations (from GenCC):

• CHARGE syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Broad Center for Mendelian Genomics, ClinGen, G2P
• hypogonadotropic hypogonadism 5 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33119243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD7	NM_017780.4	c.6079C>G	p.Arg2027Gly	missense_variant	Exon 30 of 38	ENST00000423902.7	NP_060250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD7	ENST00000423902.7	c.6079C>G	p.Arg2027Gly	missense_variant	Exon 30 of 38	5	NM_017780.4	ENSP00000392028.1
CHD7	ENST00000524602.5	c.1717-9547C>G		intron_variant	Intron 2 of 4	1		ENSP00000437061.1
CHD7	ENST00000695853.1	n.6079C>G		non_coding_transcript_exon_variant	Exon 30 of 37			ENSP00000512218.1
CHD7	ENST00000527921.1	n.*43C>G		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.46
Sift	Benign	0.18	T
Sift4G	Benign	0.084	T
Polyphen		0.0090	B
Vest4		0.34
MutPred		0.33		Loss of disorder (P = 0.0435);
MVP		0.89
MPC		1.4
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.53
gMVP		0.60
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs886040995; hg19: chr8-61765241;