2-1414438-G-GCTGGTTATGGCCTGCACAGA
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001206744.2(TPO):c.31_50dup(p.Glu17AspfsTer77) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. T10T) has been classified as Likely benign.
Frequency
Consequence
NM_001206744.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPO | NM_001206744.2 | c.31_50dup | p.Glu17AspfsTer77 | frameshift_variant | 2/17 | ENST00000329066.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPO | ENST00000329066.9 | c.31_50dup | p.Glu17AspfsTer77 | frameshift_variant | 2/17 | 1 | NM_001206744.2 | P1 | |
ENST00000650512.1 | n.646+3924_646+3925insTCTGTGCAGGCCATAACCAG | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251150Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135770
GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461740Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727148
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74304
ClinVar
Submissions by phenotype
Deficiency of iodide peroxidase Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 1994 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 09, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1323705). This premature translational stop signal has been observed in individual(s) with congenital hypothyroidism (PMID: 27525530). This variant is present in population databases (rs774713681, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Glu17Aspfs*77) in the TPO gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPO are known to be pathogenic (PMID: 11061528, 23236987, 25564141). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at