7-16797830-C-T

Variant names:

• chr7-16797830-C-T
• rs2280655
• NM_006408.4:c.331-136G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006408.4(AGR2):​c.331-136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 641,504 control chromosomes in the GnomAD database, including 3,358 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 0.11 (1929 hom., cov: 33)
  • Exomes 𝑓: 0.053 (1429 hom.)
• Consequence: AGR2 NM_006408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGR2	NM_006408.4	c.331-136G>A		intron_variant	Intron 5 of 7	ENST00000419304.7	NP_006399.1
AGR2	XM_005249581.5	c.331-136G>A		intron_variant	Intron 5 of 7		XP_005249638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGR2	ENST00000419304.7	c.331-136G>A		intron_variant	Intron 5 of 7	1	NM_006408.4	ENSP00000391490.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17202 AN: 151982 Hom.: 1924 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0881

GnomAD4 exome AF: 0.0532 AC: 26038 AN: 489404 Hom.: 1429 AF XY: 0.0508 AC XY: 13060 AN XY: 257204

African (AFR) AF: 0.288 AC: 3820 AN: 13252

American (AMR) AF: 0.0817 AC: 1630 AN: 19948

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 964 AN: 14242

East Asian (EAS) AF: 0.169 AC: 5254 AN: 31082

South Asian (SAS) AF: 0.0411 AC: 1827 AN: 44502

European-Finnish (FIN) AF: 0.0572 AC: 1971 AN: 34438

Middle Eastern (MID) AF: 0.0522 AC: 119 AN: 2278

European-Non Finnish (NFE) AF: 0.0285 AC: 8609 AN: 302578

Other (OTH) AF: 0.0681 AC: 1844 AN: 27084

GnomAD4 genome AF: 0.113 AC: 17244 AN: 152100 Hom.: 1929 Cov.: 33 AF XY: 0.113 AC XY: 8433 AN XY: 74354

African (AFR) AF: 0.286 AC: 11839 AN: 41466

American (AMR) AF: 0.0789 AC: 1205 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0672 AC: 233 AN: 3466

East Asian (EAS) AF: 0.196 AC: 1012 AN: 5170

South Asian (SAS) AF: 0.0447 AC: 215 AN: 4808

European-Finnish (FIN) AF: 0.0550 AC: 582 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1939 AN: 68012

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0634 Hom.: 270

Bravo AF: 0.125

Asia WGS AF: 0.134 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.022
DANN	Benign	0.39
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2280655; hg19: chr7-16837454;