2-10790776-TT-AG

Variant names:

• chr2-10790776-TT-AG
• NM_005742.4:c.641_642delAAinsCT
• PDIA6 p.Lys214Thr

Variant summary

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

The NM_005742.4(PDIA6):​c.641_642delAAinsCT​(p.Lys214Thr) variant causes a missense change. 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: 33)
• Consequence: PDIA6 NM_005742.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• Publications: 0 publications found

Genes affected

PDIA6 (HGNC:30168): (protein disulfide isomerase family A member 6) 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, a TRX-like domain, and a C-terminal ER-retention sequence. This protein inhibits the aggregation of misfolded proteins and exhibits both isomerase and chaperone activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005742.4. 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
	PDIA6	NM_005742.4	MANE Select	c.641_642delAAinsCT	p.Lys214Thr	missense	N/A	NP_005733.1	Q15084-1
	PDIA6	NM_001282704.2		c.797_798delAAinsCT	p.Lys266Thr	missense	N/A	NP_001269633.1	Q15084-2
	PDIA6	NM_001282705.2		c.785_786delAAinsCT	p.Lys262Thr	missense	N/A	NP_001269634.1	Q15084-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA6	ENST00000272227.8	TSL:1 MANE Select	c.641_642delAAinsCT	p.Lys214Thr	missense	N/A	ENSP00000272227.4	Q15084-1
	PDIA6	ENST00000404371.6	TSL:2	c.797_798delAAinsCT	p.Lys266Thr	missense	N/A	ENSP00000385385.2	Q15084-2
	PDIA6	ENST00000617249.4	TSL:5	c.797_798delAAinsCT	p.Lys266Thr	missense	N/A	ENSP00000481892.1	Q15084-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.1

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: chr2-10930902;