dbSNP rs10902088: MUC2:p.Asn1149Asn (chr11-1090036-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.3447T>C(p.Asn1149Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 1,611,784 control chromosomes in the GnomAD database, including 487,635 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 0.73 ( 41439 hom., cov: 33)

Exomes 𝑓: 0.78 ( 446196 hom. )

Consequence

MUC2
NM_002457.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.92

Publications

25 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=-0.63).

BP7

Synonymous conserved (PhyloP=-2.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 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.3447T>C	p.Asn1149Asn	synonymous	Exon 25 of 58	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000675028.1		c.3447T>C	p.Asn1149Asn	synonymous	Exon 25 of 30	ENSP00000502432.1	A0A6Q8PGX3
	MUC2	ENST00000361558.7	TSL:5	n.3474T>C		non_coding_transcript_exon	Exon 25 of 49

Frequencies

GnomAD3 genomes

AF:

0.733

AC:

111490

AN:

152008

Hom.:

41429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.848

Gnomad AMR

AF:

0.680

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.731

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.746

GnomAD4 exome

AF:

0.780

AC:

1137865

AN:

1459658

Hom.:

446196

Cov.:

AF XY:

0.780

AC XY:

566100

AN XY:

725998

show subpopulations

African (AFR)

AF:

0.641

AC:

21428

AN:

33454

American (AMR)

AF:

0.621

AC:

27579

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.845

AC:

22075

AN:

26114

East Asian (EAS)

AF:

0.576

AC:

22825

AN:

39632

South Asian (SAS)

AF:

0.731

AC:

62862

AN:

85942

European-Finnish (FIN)

AF:

0.764

AC:

40298

AN:

52716

Middle Eastern (MID)

AF:

0.785

AC:

4522

AN:

5762

European-Non Finnish (NFE)

AF:

0.801

AC:

889686

AN:

1111338

Other (OTH)

AF:

0.773

AC:

46590

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

15216

30433

45649

60866

76082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20682

41364

62046

82728

103410

<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:

0.733

AC:

111544

AN:

152126

Hom.:

41439

Cov.:

AF XY:

0.729

AC XY:

54223

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.637

AC:

26417

AN:

41498

American (AMR)

AF:

0.680

AC:

10395

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.856

AC:

2971

AN:

3472

East Asian (EAS)

AF:

0.581

AC:

3005

AN:

5172

South Asian (SAS)

AF:

0.731

AC:

3527

AN:

4822

European-Finnish (FIN)

AF:

0.770

AC:

8153

AN:

10594

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.802

AC:

54491

AN:

67962

Other (OTH)

AF:

0.746

AC:

1574

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1519

3037

4556

6074

7593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.778

Hom.:

77373

Bravo

AF:

0.720

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.088

(source)

PhyloP100

-2.9

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