chr15-45111501-C-T
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001363711.2(DUOX2):c.598G>A(p.Gly200Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,551,330 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.
Frequency
Consequence
NM_001363711.2 missense
Scores
Clinical Significance
Conservation
Publications
- thyroid dyshormonogenesis 6Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- familial thyroid dyshormonogenesisInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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DUOX2 | ENST00000389039.11 | c.598G>A | p.Gly200Arg | missense_variant | Exon 6 of 34 | 1 | NM_001363711.2 | ENSP00000373691.7 | ||
DUOX2 | ENST00000603300.1 | c.598G>A | p.Gly200Arg | missense_variant | Exon 6 of 34 | 1 | ENSP00000475084.1 | |||
DUOX2 | ENST00000558383.1 | n.823G>A | non_coding_transcript_exon_variant | Exon 4 of 17 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00144 AC: 219AN: 151790Hom.: 5 Cov.: 28 show subpopulations
GnomAD2 exomes AF: 0.000906 AC: 135AN: 149026 AF XY: 0.000971 show subpopulations
GnomAD4 exome AF: 0.00131 AC: 1839AN: 1399434Hom.: 12 Cov.: 32 AF XY: 0.00133 AC XY: 918AN XY: 691094 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
Age Distribution
GnomAD4 genome AF: 0.00144 AC: 219AN: 151896Hom.: 5 Cov.: 28 AF XY: 0.00132 AC XY: 98AN XY: 74262 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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Congenital hypothyroidism Pathogenic:1
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not specified Uncertain:1
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Familial thyroid dyshormonogenesis;C4749351:Genetic transient congenital hypothyroidism Uncertain:1
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Thyroid dyshormonogenesis 6 Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at