2-10823695-C-T

Variant names:

• chr2-10823695-C-T
• rs2969885
• NM_001282704.2:c.-54-2777G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001282704.2(PDIA6):​c.-54-2777G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 152,342 control chromosomes in the GnomAD database, including 5 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 0.0026 (5 hom., cov: 34)
• Consequence: PDIA6 NM_001282704.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA6	NM_001282704.2	c.-54-2777G>A		intron_variant	Intron 1 of 14		NP_001269633.1
PDIA6	NM_001282705.2	c.83-4341G>A		intron_variant	Intron 1 of 13		NP_001269634.1
PDIA6	NM_001282706.2	c.-47-4341G>A		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.-54-2777G>A		intron_variant	Intron 1 of 14	2		ENSP00000385385.2
PDIA6	ENST00000404824.2	c.83-4341G>A		intron_variant	Intron 1 of 13	2		ENSP00000384459.2
PDIA6	ENST00000381611.8	c.-47-4341G>A		intron_variant	Intron 1 of 13	2		ENSP00000371024.4
PDIA6	ENST00000458536.1	c.-813-296G>A		intron_variant	Intron 1 of 4	5		ENSP00000389558.1

Frequencies

GnomAD3 genomes AF: 0.00261 AC: 397 AN: 152224 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.00941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00261 AC: 397 AN: 152342 Hom.: 5 Cov.: 34 AF XY: 0.00256 AC XY: 191 AN XY: 74490

African (AFR) AF: 0.00938 AC: 390 AN: 41576

American (AMR) AF: 0.000261 AC: 4 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00114 Hom.: 0

Bravo AF: 0.00284

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.25
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2969885; hg19: chr2-10963821;