7-16797830-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006408.4(AGR2):​c.331-136G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000408 in 489,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: AGR2 NM_006408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGR2	NM_006408.4	c.331-136G>C		intron_variant	Intron 5 of 7	ENST00000419304.7	NP_006399.1
AGR2	XM_005249581.5	c.331-136G>C		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>C		intron_variant	Intron 5 of 7	1	NM_006408.4	ENSP00000391490.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000408 AC: 2 AN: 489608 Hom.: 0 AF XY: 0.00000389 AC XY: 1 AN XY: 257320

African (AFR) AF: 0.00 AC: 0 AN: 13274

American (AMR) AF: 0.00 AC: 0 AN: 19960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14246

East Asian (EAS) AF: 0.00 AC: 0 AN: 31106

South Asian (SAS) AF: 0.00 AC: 0 AN: 44510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2282

European-Non Finnish (NFE) AF: 0.00000330 AC: 1 AN: 302670

Other (OTH) AF: 0.0000369 AC: 1 AN: 27102

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.018
DANN	Benign	0.36
PhyloP100		-2.5

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;