chr15-45114714-AGCTTCCT-A

Position:

• chr15-45114714-AGCTTCCT-A

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_207581.4(DUOXA2):​c.113_119delTCCTGCT​(p.Phe38fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DUOXA2 NM_207581.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.59

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]

DUOXA2 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-45114714-AGCTTCCT-A is Pathogenic according to our data. Variant chr15-45114714-AGCTTCCT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3383175.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOXA2	NM_207581.4	c.113_119delTCCTGCT	p.Phe38fs	frameshift_variant	1/6	ENST00000323030.6	NP_997464.2
DUOXA2	XM_017022180.2	c.113_119delTCCTGCT	p.Phe38fs	frameshift_variant	1/6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOXA2	ENST00000323030.6	c.113_119delTCCTGCT	p.Phe38fs	frameshift_variant	1/6	1	NM_207581.4	ENSP00000319705.5
DUOXA2	ENST00000491993.2	n.113_119delTCCTGCT		non_coding_transcript_exon_variant	1/6	1		ENSP00000454110.1
DUOXA2	ENST00000350243.10	n.393_399delTCCTGCT		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Thyroglobulin synthesis defect Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Juno Genomics, Hangzhou Juno Genomics, Inc

-

PVS1+PM2_Supporting -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45406912;