11-1088404-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002457.5(MUC2):c.3102C>T(p.Pro1034=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,610,072 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (58 hom.)
• Consequence: MUC2 NM_002457.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.17

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-1088404-C-T is Benign according to our data. Variant chr11-1088404-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC2	NM_002457.5	c.3102C>T	p.Pro1034=	synonymous_variant	23/58	ENST00000713550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC2	ENST00000675028.1	c.3102C>T	p.Pro1034=	synonymous_variant	23/30			P3
MUC2	ENST00000361558.7	n.3129C>T		non_coding_transcript_exon_variant	23/49	5

Frequencies

GnomAD3 genomes AF: 0.00641 AC: 975 AN: 152196 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00576

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00668 AC: 1609 AN: 240882 Hom.: 28 AF XY: 0.00666 AC XY: 876 AN XY: 131454

Gnomad AFR exome AF: 0.000482

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000701

Gnomad FIN exome AF: 0.0412

Gnomad NFE exome AF: 0.00579

Gnomad OTH exome AF: 0.00511

GnomAD4 exome AF: 0.00504 AC: 7349 AN: 1457758 Hom.: 58 Cov.: 45 AF XY: 0.00495 AC XY: 3585 AN XY: 724960

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000676

Gnomad4 FIN exome AF: 0.0364

Gnomad4 NFE exome AF: 0.00454

Gnomad4 OTH exome AF: 0.00403

GnomAD4 genome AF: 0.00641 AC: 976 AN: 152314 Hom.: 11 Cov.: 32 AF XY: 0.00854 AC XY: 636 AN XY: 74468

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0480

Gnomad4 NFE AF: 0.00576

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00500 Hom.: 1

Bravo AF: 0.00238

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MUC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.85
Dann	Benign	0.92

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

LitVar

Other links and lift over

dbSNP: rs200179172; hg19: chr11-1086393;