rs10253216

Positions:

• chr7-16822225-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000412973.1(AGR2):​c.-98-10470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,080 control chromosomes in the GnomAD database, including 9,432 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 0.30 (9432 hom., cov: 32)
• Consequence: AGR2 ENST00000412973.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGR2	ENST00000412973.1	c.-98-10470C>T		intron_variant		5		ENSP00000411969

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45243 AN: 151962 Hom.: 9409 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.298 AC: 45314 AN: 152080 Hom.: 9432 Cov.: 32 AF XY: 0.299 AC XY: 22236 AN XY: 74364

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.286

Alfa AF: 0.189 Hom.: 2067

Bravo AF: 0.317

Asia WGS AF: 0.438 AC: 1521 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10253216; hg19: chr7-16861849;