chr2-10823401-T-C

Variant names:

• chr2-10823401-T-C
• rs1106184
• NM_001282704.2:c.-54-2483A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 5 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: 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282704.2. 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_001282704.2		c.-54-2483A>G		intron	N/A	NP_001269633.1
	PDIA6	NM_001282705.2		c.83-4047A>G		intron	N/A	NP_001269634.1
	PDIA6	NM_001282706.2		c.-47-4047A>G		intron	N/A	NP_001269635.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDIA6	ENST00000404371.6	TSL:2	c.-54-2483A>G		intron	N/A	ENSP00000385385.2
	PDIA6	ENST00000404824.2	TSL:2	c.83-4047A>G		intron	N/A	ENSP00000384459.2
	PDIA6	ENST00000381611.8	TSL:2	c.-47-4047A>G		intron	N/A	ENSP00000371024.4

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108453 AN: 152072 Hom.: 39376 Cov.: 33

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: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.713 AC: 108554 AN: 152190 Hom.: 39415 Cov.: 33 AF XY: 0.716 AC XY: 53275 AN XY: 74392

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.3
DANN	Benign	0.40
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1106184; hg19: chr2-10963527;