rs2001616
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001363711.2(DUOX2):c.413C>T(p.Pro138Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,194 control chromosomes in the GnomAD database, including 48,317 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Synonymous variant affecting the same amino acid position (i.e. P138P) has been classified as Likely benign.
Frequency
Consequence
NM_001363711.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DUOX2 | NM_001363711.2 | c.413C>T | p.Pro138Leu | missense_variant | 5/34 | ENST00000389039.11 | |
DUOX2 | NM_014080.5 | c.413C>T | p.Pro138Leu | missense_variant | 5/34 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DUOX2 | ENST00000389039.11 | c.413C>T | p.Pro138Leu | missense_variant | 5/34 | 1 | NM_001363711.2 | P4 | |
DUOX2 | ENST00000603300.1 | c.413C>T | p.Pro138Leu | missense_variant | 5/34 | 1 | A1 | ||
DUOX2 | ENST00000558383.1 | n.456C>T | non_coding_transcript_exon_variant | 4/17 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.766 AC: 116562AN: 152076Hom.: 48324 Cov.: 33
GnomAD3 exomes AF: 0.870 AC: 217090AN: 249568Hom.: 96466 AF XY: 0.880 AC XY: 119118AN XY: 135384
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.892 AC: 1303149AN: 1461378Hom.: 585879 Cov.: 85 AF XY: 0.894 AC XY: 650240AN XY: 727006
GnomAD4 genome ? AF: 0.766 AC: 116575AN: 152194Hom.: 48317 Cov.: 33 AF XY: 0.773 AC XY: 57525AN XY: 74438
ClinVar
Submissions by phenotype
Thyroid dyshormonogenesis 6 Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at