dbSNP rs2280655: AGR2:c.331-136G>T (chr7-16797830-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006408.4(AGR2):c.331-136G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 641,620 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

AGR2
NM_006408.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.52

Publications

3 publications found

Variant links:

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)

AGR2 links:

ENSG00000289189 (HGNC:):

ENSG00000289189 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGR2	NM_006408.4 link	c.331-136G>T		intron_variant	Intron 5 of 7	ENST00000419304.7	NP_006399.1	O95994Q4JM46
AGR2	XM_005249581.5 link	c.331-136G>T		intron_variant	Intron 5 of 7		XP_005249638.1	O95994Q4JM46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGR2	ENST00000419304.7 link	c.331-136G>T		intron_variant	Intron 5 of 7	1	NM_006408.4	ENSP00000391490.2		O95994

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000408

AC:

AN:

489608

Hom.:

AF XY:

0.00000389

AC XY:

AN XY:

257320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13274

American (AMR)

AF:

0.00

AC:

AN:

19960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14246

East Asian (EAS)

AF:

0.00

AC:

AN:

31106

South Asian (SAS)

AF:

0.00

AC:

AN:

44510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2282

European-Non Finnish (NFE)

AF:

0.00000661

AC:

AN:

302670

Other (OTH)

AF:

0.00

AC:

AN:

27102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41362

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000554

Hom.:

270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.017

(source)

DANN

Benign

0.37

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over