rs774230086

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006849.4(PDIA2):​c.392C>A​(p.Pro131Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PDIA2
NM_006849.4 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.54
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDIA2NM_006849.4 linkc.392C>A p.Pro131Gln missense_variant Exon 2 of 11 ENST00000219406.11 NP_006840.2 Q13087-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDIA2ENST00000219406.11 linkc.392C>A p.Pro131Gln missense_variant Exon 2 of 11 1 NM_006849.4 ENSP00000219406.7 Q13087-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459848
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.026
T;.
Eigen
Uncertain
0.21
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.80
T;T
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-4.7
D;D
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.80
P;.
Vest4
0.55
MutPred
0.55
Gain of MoRF binding (P = 0.0861);Gain of MoRF binding (P = 0.0861);
MVP
0.80
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.45
gMVP
0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-334579; API