Genetic Variant MUC2:p.Cys3513Cys (chr11-1102586-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002457.5(MUC2):c.10539C>T(p.Cys3513Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,612,546 control chromosomes in the GnomAD database, including 123,324 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 0.30 ( 8394 hom., cov: 34)

Exomes 𝑓: 0.38 ( 114930 hom. )

Consequence

MUC2
NM_002457.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0500

Publications

19 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP7

Synonymous conserved (PhyloP=0.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC2	NM_002457.5 link	c.10539C>T	p.Cys3513Cys	synonymous_variant	Exon 43 of 58		NP_002448.5	Q02817A0A3S8TMF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000674892.1 link	c.1023C>T	p.Cys341Cys	synonymous_variant	Exon 5 of 20			ENSP00000501871.1		A0A6Q8PFN2
MUC2	ENST00000361558.7 link	n.10576C>T		non_coding_transcript_exon_variant	Exon 34 of 49	5

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45623

AN:

152150

Hom.:

8391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.00577

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.385

AC:

562190

AN:

1460278

Hom.:

114930

Cov.:

AF XY:

0.381

AC XY:

276933

AN XY:

726416

show subpopulations

African (AFR)

AF:

0.105

AC:

3522

AN:

33480

American (AMR)

AF:

0.272

AC:

12169

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

9072

AN:

26136

East Asian (EAS)

AF:

0.00479

AC:

190

AN:

39672

South Asian (SAS)

AF:

0.247

AC:

21346

AN:

86256

European-Finnish (FIN)

AF:

0.434

AC:

22625

AN:

52094

Middle Eastern (MID)

AF:

0.328

AC:

1892

AN:

5768

European-Non Finnish (NFE)

AF:

0.423

AC:

469849

AN:

1111808

Other (OTH)

AF:

0.357

AC:

21525

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

25567

51135

76702

102270

127837

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13994

27988

41982

55976

69970

<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:

0.300

AC:

45645

AN:

152268

Hom.:

8394

Cov.:

AF XY:

0.299

AC XY:

22283

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.114

AC:

4722

AN:

41582

American (AMR)

AF:

0.292

AC:

4474

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1203

AN:

3472

East Asian (EAS)

AF:

0.00598

AC:

AN:

5184

South Asian (SAS)

AF:

0.236

AC:

1141

AN:

4826

European-Finnish (FIN)

AF:

0.424

AC:

4498

AN:

10612

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.417

AC:

28377

AN:

67980

Other (OTH)

AF:

0.304

AC:

642

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1634

3268

4902

6536

8170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.379

Hom.:

23004

Bravo

AF:

0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

7.7

(source)

PhyloP100

0.050

Splicing

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