chr15-45114723-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_207581.4(DUOXA2):c.118C>T(p.Leu40Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,614,224 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00053 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00082 ( 19 hom. )
Consequence
DUOXA2
NM_207581.4 missense
NM_207581.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -0.00600
Genes affected
DUOXA2 (HGNC:32698): (dual oxidase maturation factor 2) This gene encodes an endoplasmic reticulum protein that is necessary for proper cellular localization and maturation of functional dual oxidase 2. Mutations in this gene have been associated with thyroid dyshormonogenesis 5.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007504195).
BP6
?
Variant 15-45114723-C-T is Benign according to our data. Variant chr15-45114723-C-T is described in ClinVar as [Benign]. Clinvar id is 744450.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000525 (80/152344) while in subpopulation SAS AF= 0.0164 (79/4824). AF 95% confidence interval is 0.0135. There are 4 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DUOXA2 | NM_207581.4 | c.118C>T | p.Leu40Phe | missense_variant | 1/6 | ENST00000323030.6 | |
DUOXA2 | XM_017022180.2 | c.118C>T | p.Leu40Phe | missense_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DUOXA2 | ENST00000323030.6 | c.118C>T | p.Leu40Phe | missense_variant | 1/6 | 1 | NM_207581.4 | P1 | |
DUOXA2 | ENST00000491993.2 | c.118C>T | p.Leu40Phe | missense_variant, NMD_transcript_variant | 1/6 | 1 | |||
DUOXA2 | ENST00000350243.10 | n.398C>T | non_coding_transcript_exon_variant | 1/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000532 AC: 81AN: 152224Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00167 AC: 420AN: 251472Hom.: 7 AF XY: 0.00219 AC XY: 297AN XY: 135916
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GnomAD4 exome AF: 0.000822 AC: 1201AN: 1461880Hom.: 19 Cov.: 31 AF XY: 0.00120 AC XY: 871AN XY: 727244
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GnomAD4 genome ? AF: 0.000525 AC: 80AN: 152344Hom.: 4 Cov.: 32 AF XY: 0.000819 AC XY: 61AN XY: 74498
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of MoRF binding (P = 0.13);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at