GeneBe

NM_017780.4:c.8744delG

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_017780.4(CHD7):​c.8744delG​(p.Gly2915AspfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,366 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CHD7
NM_017780.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

0 publications found
Variant links:
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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, ClinGen
  • 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CHD7
NM_017780.4
MANE Select
c.8744delGp.Gly2915AspfsTer2
frameshift
Exon 38 of 38NP_060250.2
CHD7
NM_001316690.1
c.2597delGp.Gly866AspfsTer2
frameshift
Exon 5 of 5NP_001303619.1Q9P2D1-4

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CHD7
ENST00000423902.7
TSL:5 MANE Select
c.8744delGp.Gly2915AspfsTer2
frameshift
Exon 38 of 38ENSP00000392028.1Q9P2D1-1
CHD7
ENST00000524602.5
TSL:1
c.2597delGp.Gly866AspfsTer2
frameshift
Exon 5 of 5ENSP00000437061.1Q9P2D1-4
CHD7
ENST00000933299.1
c.8777delGp.Gly2926AspfsTer2
frameshift
Exon 38 of 38ENSP00000603358.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1454366
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
722424
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33162
American (AMR)
AF:
0.00
AC:
0
AN:
44240
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25746
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39576
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53196
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5732
European-Non Finnish (NFE)
AF:
9.03e-7
AC:
1
AN:
1106910
Other (OTH)
AF:
0.00
AC:
0
AN:
59980
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.5

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1554607313; hg19: chr8-61778236; COSMIC: COSV71108188; COSMIC: COSV71108188; API