rs10253216

Variant names:

• chr7-16822225-G-A
• rs10253216
• ENST00000412973.1:c.-98-10470C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

AGR2 Gene-Disease associations (from GenCC):

• respiratory infections, recurrent, and failure to thrive with or without diarrhea

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000289189 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGR2	ENST00000412973.1	c.-98-10470C>T		intron_variant	Intron 1 of 6	5		ENSP00000411969.1
ENSG00000289189	ENST00000766377.1	n.211+4852G>A		intron_variant	Intron 2 of 3

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

African (AFR) AF: 0.572 AC: 23704 AN: 41468

American (AMR) AF: 0.246 AC: 3753 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2742 AN: 5154

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1911 AN: 10588

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10371 AN: 67980

Other (OTH) AF: 0.286 AC: 601 AN: 2104

Alfa AF: 0.221 Hom.: 5235

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10253216; hg19: chr7-16861849;