dbSNP rs112894065: MUC2:p.Thr1445Thr (chr11-1094578-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_002457.5(MUC2):c.4335G>A(p.Thr1445Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1445T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MUC2
NM_002457.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.20

Publications

1 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:

ENSG00000296903 (HGNC:):

ENSG00000296903 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-3.2 with no splicing effect.

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.4335G>A	p.Thr1445Thr	synonymous	Exon 30 of 58	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MUC2	ENST00000361558.7	TSL:5	n.4362G>A	non_coding_transcript_exon	Exon 30 of 49
ENSG00000296903	ENST00000743440.1		n.141-257C>T	intron	N/A
MUC2	ENST00000675028.1		c.*153G>A	downstream_gene	N/A	ENSP00000502432.1	A0A6Q8PGX3

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

AN:

4906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00180

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00725

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00203

AC:

AN:

6404

AF XY:

0.00259

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00955

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000107

AC:

AN:

570964

Hom.:

Cov.:

AF XY:

0.0000987

AC XY:

AN XY:

273672

show subpopulations

African (AFR)

AF:

0.000238

AC:

AN:

12608

American (AMR)

AF:

0.000126

AC:

AN:

7918

Ashkenazi Jewish (ASJ)

AF:

0.000142

AC:

AN:

7024

East Asian (EAS)

AF:

0.000765

AC:

AN:

7846

South Asian (SAS)

AF:

0.000189

AC:

AN:

26496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13066

Middle Eastern (MID)

AF:

0.00152

AC:

AN:

1320

European-Non Finnish (NFE)

AF:

0.0000845

AC:

AN:

473186

Other (OTH)

AF:

0.000140

AC:

AN:

21500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00244

AC:

AN:

4926

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

AN XY:

2436

show subpopulations

African (AFR)

AF:

0.00268

AC:

AN:

1120

American (AMR)

AF:

0.00177

AC:

AN:

564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

108

East Asian (EAS)

AF:

0.00714

AC:

AN:

140

South Asian (SAS)

AF:

0.00

AC:

AN:

154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00306

AC:

AN:

2288

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.404

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000135

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.061

(source)

DANN

Benign

0.26

PhyloP100

-3.2

Mutation Taster

=100/0

polymorphism

(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

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