Genetic Variant PDIA6:c.-54-2483A>G (chr2-10823401-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001282704.2(PDIA6):c.-54-2483A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,196 control chromosomes in the GnomAD database, including 39,415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 39415 hom., cov: 33)

Exomes 𝑓: 0.33 ( 0 hom. )

Consequence

PDIA6
NM_001282704.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.120

Publications

5 publications found

Variant links:

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]

PDIA6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PDIA6	NM_001282704.2 link	c.-54-2483A>G	intron_variant	Intron 1 of 14	NP_001269633.1	Q15084-2
PDIA6	NM_001282705.2 link	c.83-4047A>G	intron_variant	Intron 1 of 13	NP_001269634.1	Q15084-5
PDIA6	NM_001282706.2 link	c.-47-4047A>G	intron_variant	Intron 1 of 13	NP_001269635.1	Q15084-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PDIA6	ENST00000404371.6 link	c.-54-2483A>G	intron_variant	Intron 1 of 14	2	ENSP00000385385.2	Q15084-2
PDIA6	ENST00000404824.2 link	c.83-4047A>G	intron_variant	Intron 1 of 13	2	ENSP00000384459.2	Q15084-5
PDIA6	ENST00000381611.8 link	c.-47-4047A>G	intron_variant	Intron 1 of 13	2	ENSP00000371024.4	Q15084-4
PDIA6	ENST00000458536.1 link	c.-813-2A>G	splice_acceptor_variant, intron_variant	Intron 1 of 4	5	ENSP00000389558.1	C9JNG5

Frequencies

GnomAD3 genomes

AF:

0.713

AC:

108453

AN:

152072

Hom.:

39376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.848

Gnomad AMI

AF:

0.750

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.673

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.634

Gnomad OTH

AF:

0.703

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.713

AC:

108554

AN:

152190

Hom.:

39415

Cov.:

AF XY:

0.716

AC XY:

53275

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.848

AC:

35233

AN:

41526

American (AMR)

AF:

0.705

AC:

10773

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

2457

AN:

3468

East Asian (EAS)

AF:

0.799

AC:

4138

AN:

5176

South Asian (SAS)

AF:

0.696

AC:

3357

AN:

4822

European-Finnish (FIN)

AF:

0.673

AC:

7121

AN:

10586

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.634

AC:

43089

AN:

68002

Other (OTH)

AF:

0.706

AC:

1493

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1527

3053

4580

6106

7633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.665

Hom.:

44232

Bravo

AF:

0.722

Asia WGS

AF:

0.760

AC:

2645

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

7.3

(source)

DANN

Benign

0.40

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over