2-10823401-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA6	NM_001282704.2	c.-54-2483A>G		intron_variant	Intron 1 of 14		NP_001269633.1
PDIA6	NM_001282705.2	c.83-4047A>G		intron_variant	Intron 1 of 13		NP_001269634.1
PDIA6	NM_001282706.2	c.-47-4047A>G		intron_variant	Intron 1 of 13		NP_001269635.1

Ensembl

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

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

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.706

Alfa AF: 0.657 Hom.: 33325

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
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1106184; hg19: chr2-10963527;