chr7-16794986-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3PP5
The NM_006408.4(AGR2):c.428G>A(p.Gly143Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
AGR2
NM_006408.4 missense
NM_006408.4 missense
Scores
7
11
1
Clinical Significance
Conservation
PhyloP100: 7.32
Genes affected
AGR2 (HGNC:328): (anterior gradient 2, protein disulphide isomerase family member) 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, a catalytically active thioredoxin domain, and a C-terminal ER-retention sequence. This protein plays a role in cell migration, cellular transformation and metastasis and is as a p53 inhibitor. As an ER-localized molecular chaperone, it plays a role in the folding, trafficking, and assembly of cysteine-rich transmembrane receptors and the cysteine-rich intestinal gylcoprotein mucin. This gene has been implicated in inflammatory bowel disease and cancer progression. [provided by RefSeq, Mar 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
In a chain Anterior gradient protein 2 homolog (size 154) in uniprot entity AGR2_HUMAN there are 8 pathogenic changes around while only 1 benign (89%) in NM_006408.4
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.821
PP5
Variant 7-16794986-C-T is Pathogenic according to our data. Variant chr7-16794986-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2443888.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-16794986-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGR2 | NM_006408.4 | c.428G>A | p.Gly143Glu | missense_variant | 7/8 | ENST00000419304.7 | |
AGR2 | XM_005249581.5 | c.428G>A | p.Gly143Glu | missense_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGR2 | ENST00000419304.7 | c.428G>A | p.Gly143Glu | missense_variant | 7/8 | 1 | NM_006408.4 | P1 | |
AGR2 | ENST00000401412.5 | c.428G>A | p.Gly143Glu | missense_variant | 7/7 | 2 | |||
AGR2 | ENST00000450569.5 | c.218G>A | p.Gly73Glu | missense_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461808Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727214
GnomAD4 exome
AF:
AC:
15
AN:
1461808
Hom.:
Cov.:
34
AF XY:
AC XY:
6
AN XY:
727214
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Respiratory infections, recurrent, and failure to thrive with or without diarrhea Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 31, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of methylation at R144 (P = 0.0515);.;Loss of methylation at R144 (P = 0.0515);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at