7-16797830-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• 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/exons	MANE	UniProt
AGR2	NM_006408.4	c.331-136G>A		intron_variant		ENST00000419304.7
AGR2	XM_005249581.5	c.331-136G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGR2	ENST00000419304.7	c.331-136G>A		intron_variant		1	NM_006408.4	P1
AGR2	ENST00000401412.5	c.331-136G>A		intron_variant		2
AGR2	ENST00000412973.1	c.331-136G>A		intron_variant		5
AGR2	ENST00000450569.5	c.121-136G>A		intron_variant		5

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

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.0817

Gnomad4 ASJ exome AF: 0.0677

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.0411

Gnomad4 FIN exome AF: 0.0572

Gnomad4 NFE exome AF: 0.0285

Gnomad4 OTH exome AF: 0.0681

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

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.0447

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0943

Alfa AF: 0.0649 Hom.: 159

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2280655; hg19: chr7-16837454;