Genetic Variant MUC2:p.Pro3894Pro (chr11-1107741-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002457.5(MUC2):c.11682T>C(p.Pro3894Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,612,670 control chromosomes in the GnomAD database, including 240,236 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 0.56 ( 24937 hom., cov: 33)

Exomes 𝑓: 0.53 ( 215299 hom. )

Consequence

MUC2
NM_002457.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.47

Publications

18 publications found

Variant links:

COSMIC-nc: COSV64212278

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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new If you want to explore the variant's impact on the transcript NM_002457.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP7

Synonymous conserved (PhyloP=-2.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002457.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	NM_002457.5	MANE Select	c.11682T>C	p.Pro3894Pro	synonymous	Exon 51 of 58	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000674892.1		c.2166T>C	p.Pro722Pro	synonymous	Exon 13 of 20	ENSP00000501871.1	A0A6Q8PFN2
	MUC2	ENST00000361558.7	TSL:5	n.11719T>C		non_coding_transcript_exon	Exon 42 of 49

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85653

AN:

152012

Hom.:

24896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.620

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.993

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.545

GnomAD2 exomes

AF:

0.584

AC:

144845

AN:

248048

AF XY:

0.577

show subpopulations

Gnomad AFR exome

AF:

0.624

Gnomad AMR exome

AF:

0.653

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.534

AC:

779752

AN:

1460538

Hom.:

215299

Cov.:

AF XY:

0.535

AC XY:

388420

AN XY:

726550

show subpopulations

African (AFR)

AF:

0.626

AC:

20971

AN:

33476

American (AMR)

AF:

0.645

AC:

28835

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

10768

AN:

26130

East Asian (EAS)

AF:

0.994

AC:

39473

AN:

39694

South Asian (SAS)

AF:

0.617

AC:

53256

AN:

86254

European-Finnish (FIN)

AF:

0.563

AC:

29647

AN:

52642

Middle Eastern (MID)

AF:

0.480

AC:

2769

AN:

5764

European-Non Finnish (NFE)

AF:

0.505

AC:

561034

AN:

1111520

Other (OTH)

AF:

0.547

AC:

32999

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

19887

39774

59661

79548

99435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16500

33000

49500

66000

82500

<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:

0.564

AC:

85757

AN:

152132

Hom.:

24937

Cov.:

AF XY:

0.568

AC XY:

42248

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.620

AC:

25734

AN:

41518

American (AMR)

AF:

0.576

AC:

8810

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1363

AN:

3468

East Asian (EAS)

AF:

0.993

AC:

5120

AN:

5158

South Asian (SAS)

AF:

0.636

AC:

3070

AN:

4826

European-Finnish (FIN)

AF:

0.534

AC:

5660

AN:

10598

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.507

AC:

34445

AN:

67950

Other (OTH)

AF:

0.550

AC:

1162

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1896

3793

5689

7586

9482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.519

Hom.:

47021

Bravo

AF:

0.571

Asia WGS

AF:

0.833

AC:

2897

AN:

3478

EpiCase

AF:

0.494

EpiControl

AF:

0.490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.12

(source)

DANN

Benign

0.34

PhyloP100

-2.5

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over