rs1106184

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-10823401-T-A
• chr2-10823401-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282704.2(PDIA6):​c.-54-2483A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDIA6	NM_001282704.2	c.-54-2483A>T		intron_variant	Intron 1 of 14		NP_001269633.1
PDIA6	NM_001282705.2	c.83-4047A>T		intron_variant	Intron 1 of 13		NP_001269634.1
PDIA6	NM_001282706.2	c.-47-4047A>T		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>T		intron_variant	Intron 1 of 14	2		ENSP00000385385.2
PDIA6	ENST00000404824.2	c.83-4047A>T		intron_variant	Intron 1 of 13	2		ENSP00000384459.2
PDIA6	ENST00000381611.8	c.-47-4047A>T		intron_variant	Intron 1 of 13	2		ENSP00000371024.4
PDIA6	ENST00000458536.1	c.-813-2A>T		splice_acceptor_variant, intron_variant	Intron 1 of 4	5		ENSP00000389558.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.6
DANN	Benign	0.39

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;