dbSNP rs11245936: MUC2:p.Gly832Ser (chr11-1086366-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BA1

The NM_002457.5(MUC2):c.2494G>A(p.Gly832Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0823 in 1,613,088 control chromosomes in the GnomAD database, including 5,881 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.070 ( 413 hom., cov: 33)

Exomes 𝑓: 0.084 ( 5468 hom. )

Consequence

MUC2
NM_002457.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.59

Publications

26 publications found

Variant links:

Genes affected

MUC2 (HGNC:7512): (mucin 2, oligomeric mucus/gel-forming) This gene encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins produced by many epithelial tissues. The protein encoded by this gene is secreted and forms an insoluble mucous barrier that protects the gut lumen. The protein polymerizes into a gel of which 80% is composed of oligosaccharide side chains by weight. The protein features a central domain containing tandem repeats rich in threonine and proline that varies between 50 and 115 copies in different individuals. Downregulation of this gene has been observed in patients with Crohn disease and ulcerative colitis. [provided by RefSeq, Oct 2016]

MUC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC2	NM_002457.5 link	c.2494G>A	p.Gly832Ser	missense_variant	Exon 19 of 58	ENST00000713550.1	NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000675028.1 link	c.2494G>A	p.Gly832Ser	missense_variant	Exon 19 of 30			ENSP00000502432.1
MUC2	ENST00000361558.7 link	n.2521G>A		non_coding_transcript_exon_variant	Exon 19 of 49	5

Frequencies

GnomAD3 genomes

AF:

0.0696

AC:

10593

AN:

152124

Hom.:

413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.0452

Gnomad AMR

AF:

0.0517

Gnomad ASJ

AF:

0.0404

Gnomad EAS

AF:

0.0603

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0897

Gnomad OTH

AF:

0.0664

GnomAD2 exomes

AF:

0.0706

AC:

17500

AN:

247974

AF XY:

0.0710

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.0358

Gnomad ASJ exome

AF:

0.0454

Gnomad EAS exome

AF:

0.0641

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0856

Gnomad OTH exome

AF:

0.0722

GnomAD4 exome

AF:

0.0836

AC:

122186

AN:

1460846

Hom.:

5468

Cov.:

AF XY:

0.0828

AC XY:

60154

AN XY:

726688

show subpopulations

African (AFR)

AF:

0.0413

AC:

1383

AN:

33480

American (AMR)

AF:

0.0382

AC:

1707

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0448

AC:

1171

AN:

26132

East Asian (EAS)

AF:

0.0449

AC:

1783

AN:

39680

South Asian (SAS)

AF:

0.0522

AC:

4501

AN:

86252

European-Finnish (FIN)

AF:

0.114

AC:

5990

AN:

52684

Middle Eastern (MID)

AF:

0.0328

AC:

189

AN:

5766

European-Non Finnish (NFE)

AF:

0.0906

AC:

100706

AN:

1111792

Other (OTH)

AF:

0.0788

AC:

4756

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

6902

13804

20707

27609

34511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3654

7308

10962

14616

18270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0696

AC:

10596

AN:

152242

Hom.:

413

Cov.:

AF XY:

0.0695

AC XY:

5173

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0396

AC:

1645

AN:

41546

American (AMR)

AF:

0.0516

AC:

790

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0404

AC:

140

AN:

3468

East Asian (EAS)

AF:

0.0605

AC:

313

AN:

5176

South Asian (SAS)

AF:

0.0472

AC:

228

AN:

4832

European-Finnish (FIN)

AF:

0.113

AC:

1192

AN:

10594

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0897

AC:

6102

AN:

68004

Other (OTH)

AF:

0.0658

AC:

139

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

523

1046

1570

2093

2616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0792

Hom.:

2069

Bravo

AF:

0.0640

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

EpiCase

AF:

0.0857

EpiControl

AF:

0.0804

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

0.99

PhyloP100

5.6

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.66

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.66

Position offset: 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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over