16-285372-ACG-CGT

Variant names:

• chr16-285372-ACG-CGT
• NM_006849.4:c.856_858delACGinsCGT
• PDIA2 p.Thr286Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006849.4(PDIA2):​c.856_858delACGinsCGT​(p.Thr286Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDIA2 NM_006849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 0 publications found

Genes affected

PDIA2 (HGNC:14180): (protein disulfide isomerase family A member 2) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, two catalytically active thioredoxin (TRX) domains, two TRX-like domains and a C-terminal ER-retention sequence. The protein plays a role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds through its thiol isomerase, oxidase, and reductase activity. The encoded protein also possesses estradiol-binding activity and can modulate intracellular estradiol levels. [provided by RefSeq, Sep 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006849.4. 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
	PDIA2	NM_006849.4	MANE Select	c.856_858delACGinsCGT	p.Thr286Arg	missense	N/A	NP_006840.2	Q13087-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA2	ENST00000219406.11	TSL:1 MANE Select	c.856_858delACGinsCGT	p.Thr286Arg	missense	N/A	ENSP00000219406.7	Q13087-1
	PDIA2	ENST00000482665.1	TSL:1	n.1071_1073delACGinsCGT		non_coding_transcript_exon	Exon 3 of 7
	PDIA2	ENST00000404312.5	TSL:5	c.847_849delACGinsCGT	p.Thr283Arg	missense	N/A	ENSP00000384410.1	Q13087-2

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-335372;