rs2685127

Variant names:

• chr16-285373-C-G
• rs2685127
• NM_006849.4:c.857C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-285373-C-G
• chr16-285373-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006849.4(PDIA2):​c.857C>G​(p.Thr286Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,580 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PDIA2 NM_006849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 29 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 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
PDIA2	NM_006849.4	c.857C>G	p.Thr286Arg	missense_variant	Exon 6 of 11	ENST00000219406.11	NP_006840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDIA2	ENST00000219406.11	c.857C>G	p.Thr286Arg	missense_variant	Exon 6 of 11	1	NM_006849.4	ENSP00000219406.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460580 Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0 AN XY: 726598

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4565

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		2.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.072
Sift	Benign	0.051	T;T
Sift4G	Benign	0.088	T;T
Polyphen		0.51	P;.
Vest4		0.27
MutPred		0.46		Gain of MoRF binding (P = 0.0854);.;
MVP		0.60
ClinPred		0.91	D
GERP RS		3.9
PromoterAI		0.0056	Neutral
Varity_R		0.57
gMVP		0.87
Mutation Taster		=93/7	polymorphism

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: rs2685127; hg19: chr16-335373;