chr2-47073815-G-GC
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_020458.4(TTC7A):c.2470dupC(p.Gln824ProfsTer11) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000547 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
TTC7A
NM_020458.4 frameshift
NM_020458.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.15
Publications
1 publications found
Genes affected
TTC7A (HGNC:19750): (tetratricopeptide repeat domain 7A) This gene encodes a protein containing tetratricopeptide repeats. Mutations in this gene disrupt intestinal development and can cause early onset inflammatory bowel disease and intestinal atresia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
ENSG00000273269 (HGNC:):
STPG4 (HGNC:26850): (sperm-tail PG-rich repeat containing 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in DNA demethylation of male pronucleus and positive regulation of DNA demethylation. Predicted to act upstream of or within C-5 methylation of cytosine. Predicted to be located in cytoplasm and nucleus. Predicted to be active in female pronucleus; germinal vesicle; and male pronucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 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;
PP5
Variant 2-47073815-G-GC is Pathogenic according to our data. Variant chr2-47073815-G-GC is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 528461.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_020458.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TTC7A | MANE Select | c.2470dupC | p.Gln824ProfsTer11 | frameshift | Exon 20 of 20 | NP_065191.2 | Q9ULT0-1 | ||
| TTC7A | c.2542dupC | p.Gln848ProfsTer11 | frameshift | Exon 21 of 21 | NP_001275880.1 | Q9ULT0-4 | |||
| TTC7A | c.2368dupC | p.Gln790ProfsTer11 | frameshift | Exon 21 of 21 | NP_001275882.1 | G5E9G4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TTC7A | TSL:2 MANE Select | c.2470dupC | p.Gln824ProfsTer11 | frameshift | Exon 20 of 20 | ENSP00000316699.5 | Q9ULT0-1 | ||
| TTC7A | TSL:1 | c.2542dupC | p.Gln848ProfsTer11 | frameshift | Exon 21 of 21 | ENSP00000378320.2 | Q9ULT0-4 | ||
| TTC7A | TSL:1 | n.*2219dupC | non_coding_transcript_exon | Exon 21 of 21 | ENSP00000386521.1 | H0Y3V7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250636 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250636
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461360Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727014 show subpopulations
GnomAD4 exome
AF:
AC:
8
AN:
1461360
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
727014
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26118
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
0
AN:
53014
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
8
AN:
1111946
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
1
-
-
Multiple gastrointestinal atresias (1)
-
1
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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