16-283220-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006849.4(PDIA2):c.51G>A(p.Ser17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,607,864 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (3 hom.)
• Consequence: PDIA2 NM_006849.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-283220-G-A is Benign according to our data. Variant chr16-283220-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645778.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDIA2	NM_006849.4	c.51G>A	p.Ser17=	synonymous_variant	1/11	ENST00000219406.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDIA2	ENST00000219406.11	c.51G>A	p.Ser17=	synonymous_variant	1/11	1	NM_006849.4	P2
PDIA2	ENST00000404312.5	c.51G>A	p.Ser17=	synonymous_variant	1/11	5		A2
PDIA2	ENST00000456379.1	c.42G>A	p.Ser14=	synonymous_variant	1/5	5
PDIA2	ENST00000467212.5	n.57G>A		non_coding_transcript_exon_variant	1/10	2

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 200 AN: 152170 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000920 AC: 222 AN: 241274 Hom.: 0 AF XY: 0.000833 AC XY: 110 AN XY: 132068

Gnomad AFR exome AF: 0.000545

Gnomad AMR exome AF: 0.000947

Gnomad ASJ exome AF: 0.00144

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000144

Gnomad NFE exome AF: 0.00145

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.00160 AC: 2335 AN: 1455576 Hom.: 3 Cov.: 32 AF XY: 0.00151 AC XY: 1096 AN XY: 723760

Gnomad4 AFR exome AF: 0.000420

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.000115

Gnomad4 NFE exome AF: 0.00192

Gnomad4 OTH exome AF: 0.00170

GnomAD4 genome AF: 0.00131 AC: 200 AN: 152288 Hom.: 1 Cov.: 33 AF XY: 0.00142 AC XY: 106 AN XY: 74460

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000770 Hom.: 0

Bravo AF: 0.00145

EpiCase AF: 0.00110

EpiControl AF: 0.00191

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

PDIA2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.22
Dann	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs372717662; hg19: chr16-333220;