rs61730032

Variant names:

• chr15-45095942-G-A
• rs61730032
• NM_001363711.2:c.3966C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-45095942-G-A
• chr15-45095942-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001363711.2(DUOX2):​c.3966C>T​(p.Ser1322Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,613,966 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (84 hom., cov: 31)
  • Exomes 𝑓: 0.016 (275 hom.)
• Consequence: DUOX2 NM_001363711.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.24
• Publications: 2 publications found

Genes affected

DUOX2 (HGNC:13273): (dual oxidase 2) The protein encoded by this gene is a glycoprotein and a member of the NADPH oxidase family. The synthesis of thyroid hormone is catalyzed by a protein complex located at the apical membrane of thyroid follicular cells. This complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes this encoded protein and DUOX1. This protein is known as dual oxidase because it has both a peroxidase homology domain and a gp91phox domain. [provided by RefSeq, Jul 2008]

DUOX2 Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-45095942-G-A is Benign according to our data. Variant chr15-45095942-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363711.2. 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
	DUOX2	NM_001363711.2	MANE Select	c.3966C>T	p.Ser1322Ser	synonymous	Exon 30 of 34	NP_001350640.1	X6RAN8
	DUOX2	NM_014080.5		c.3966C>T	p.Ser1322Ser	synonymous	Exon 30 of 34	NP_054799.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX2	ENST00000389039.11	TSL:1 MANE Select	c.3966C>T	p.Ser1322Ser	synonymous	Exon 30 of 34	ENSP00000373691.7	X6RAN8
	DUOX2	ENST00000603300.1	TSL:1	c.3966C>T	p.Ser1322Ser	synonymous	Exon 30 of 34	ENSP00000475084.1	Q9NRD8

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3805 AN: 151958 Hom.: 84 Cov.: 31

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.00461

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0149 AC: 3737 AN: 251476 AF XY: 0.0142

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.00526

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.0252

Gnomad FIN exome AF: 0.00504

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.0156 AC: 22858 AN: 1461890 Hom.: 275 Cov.: 32 AF XY: 0.0153 AC XY: 11101 AN XY: 727248

African (AFR) AF: 0.0598 AC: 2002 AN: 33478

American (AMR) AF: 0.00604 AC: 270 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00532 AC: 139 AN: 26136

East Asian (EAS) AF: 0.0385 AC: 1527 AN: 39700

South Asian (SAS) AF: 0.0116 AC: 1002 AN: 86258

European-Finnish (FIN) AF: 0.00569 AC: 304 AN: 53420

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.0149 AC: 16536 AN: 1112010

Other (OTH) AF: 0.0174 AC: 1048 AN: 60396

GnomAD4 genome AF: 0.0251 AC: 3820 AN: 152076 Hom.: 84 Cov.: 31 AF XY: 0.0241 AC XY: 1792 AN XY: 74344

African (AFR) AF: 0.0579 AC: 2402 AN: 41458

American (AMR) AF: 0.0111 AC: 169 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.0234 AC: 121 AN: 5160

South Asian (SAS) AF: 0.0119 AC: 57 AN: 4794

European-Finnish (FIN) AF: 0.00461 AC: 49 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0141 AC: 957 AN: 67976

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.0199 Hom.: 17

Bravo AF: 0.0267

Asia WGS AF: 0.0360 AC: 127 AN: 3478

EpiCase AF: 0.0130

EpiControl AF: 0.0101

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Thyroid dyshormonogenesis 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.094
DANN	Benign	0.60
PhyloP100		-2.2
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61730032; hg19: chr15-45388140; COSMIC: COSV66534157; COSMIC: COSV66534157;