chr2-10823401-T-A
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The ENST00000458536.1(PDIA6):c.-813-2A>T variant causes a splice acceptor 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
ENST00000458536.1 splice_acceptor
ENST00000458536.1 splice_acceptor
Scores
2
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 8.205882 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5, offset of 3, new splice context is: tctcccactttattctgaAGttc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDIA6 | NM_001282704.2 | c.-54-2483A>T | intron_variant | ||||
PDIA6 | NM_001282705.2 | c.83-4047A>T | intron_variant | ||||
PDIA6 | NM_001282706.2 | c.-47-4047A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDIA6 | ENST00000458536.1 | c.-813-2A>T | splice_acceptor_variant | 5 | |||||
PDIA6 | ENST00000381611.8 | c.-47-4047A>T | intron_variant | 2 | |||||
PDIA6 | ENST00000404371.6 | c.-54-2483A>T | intron_variant | 2 | |||||
PDIA6 | ENST00000404824.2 | c.83-4047A>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at