rs2856111

Positions:

• chr11-1075747-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002457.5(MUC2):​c.173C>T​(p.Pro58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,609,964 control chromosomes in the GnomAD database, including 581,143 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (48650 hom., cov: 35)
  • Exomes 𝑓: 0.85 (532493 hom.)
• Consequence: MUC2 NM_002457.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC2	NM_002457.5	c.173C>T	p.Pro58Leu	missense_variant	2/58	ENST00000713550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC2	ENST00000675028.1	c.173C>T	p.Pro58Leu	missense_variant	2/30			P3
MUC2	ENST00000361558.7	n.200C>T		non_coding_transcript_exon_variant	2/49	5

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120367 AN: 152094 Hom.: 48625 Cov.: 35

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.852 AC: 1242079 AN: 1457750 Hom.: 532493 Cov.: 75 AF XY: 0.852 AC XY: 617823 AN XY: 724918

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.872

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.832

Gnomad4 FIN exome AF: 0.826

Gnomad4 NFE exome AF: 0.872

Gnomad4 OTH exome AF: 0.839

GnomAD4 genome AF: 0.791 AC: 120452 AN: 152214 Hom.: 48650 Cov.: 35 AF XY: 0.790 AC XY: 58807 AN XY: 74424

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.880

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.828

Alfa AF: 0.854 Hom.: 81159

Bravo AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2856111; hg19: chr11-1075747;