Genetic Variant MUC2:p.Asp872Asp (chr11-1086825-C-T) – 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.2616C>T(p.Asp872Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,604,116 control chromosomes in the GnomAD database, including 479,497 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 0.71 ( 39597 hom., cov: 31)

Exomes 𝑓: 0.78 ( 439900 hom. )

Consequence

MUC2
NM_002457.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.552

Publications

23 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=-0.552 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 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.2616C>T	p.Asp872Asp	synonymous	Exon 20 of 58	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000675028.1		c.2616C>T	p.Asp872Asp	synonymous	Exon 20 of 30	ENSP00000502432.1	A0A6Q8PGX3
	MUC2	ENST00000361558.7	TSL:5	n.2643C>T		non_coding_transcript_exon	Exon 20 of 49

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108540

AN:

151888

Hom.:

39591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.576

Gnomad AMI

AF:

0.865

Gnomad AMR

AF:

0.669

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.579

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.800

Gnomad OTH

AF:

0.730

GnomAD4 exome

AF:

0.776

AC:

1126565

AN:

1452110

Hom.:

439900

Cov.:

AF XY:

0.776

AC XY:

560025

AN XY:

721472

show subpopulations

African (AFR)

AF:

0.576

AC:

19188

AN:

33318

American (AMR)

AF:

0.619

AC:

26778

AN:

43248

Ashkenazi Jewish (ASJ)

AF:

0.842

AC:

21868

AN:

25986

East Asian (EAS)

AF:

0.580

AC:

22824

AN:

39338

South Asian (SAS)

AF:

0.729

AC:

61635

AN:

84506

European-Finnish (FIN)

AF:

0.763

AC:

39768

AN:

52130

Middle Eastern (MID)

AF:

0.788

AC:

4532

AN:

5754

European-Non Finnish (NFE)

AF:

0.798

AC:

883959

AN:

1107772

Other (OTH)

AF:

0.766

AC:

46013

AN:

60058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

15432

30865

46297

61730

77162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20612

41224

61836

82448

103060

<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:

0.714

AC:

108591

AN:

152006

Hom.:

39597

Cov.:

AF XY:

0.712

AC XY:

52867

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.576

AC:

23856

AN:

41420

American (AMR)

AF:

0.669

AC:

10220

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.850

AC:

2950

AN:

3470

East Asian (EAS)

AF:

0.578

AC:

2977

AN:

5150

South Asian (SAS)

AF:

0.738

AC:

3557

AN:

4822

European-Finnish (FIN)

AF:

0.767

AC:

8119

AN:

10588

Middle Eastern (MID)

AF:

0.806

AC:

237

AN:

294

European-Non Finnish (NFE)

AF:

0.800

AC:

54344

AN:

67956

Other (OTH)

AF:

0.731

AC:

1542

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1506

3012

4519

6025

7531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.774

Hom.:

23085

Bravo

AF:

0.699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.52

(source)

PhyloP100

-0.55

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over