11-1086825-C-T

Position:

• chr11-1086825-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002457.5(MUC2):​c.2616C>T​(p.Asp872=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC2	NM_002457.5	c.2616C>T	p.Asp872=	synonymous_variant	20/58	ENST00000713550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC2	ENST00000675028.1	c.2616C>T	p.Asp872=	synonymous_variant	20/30			P3
MUC2	ENST00000361558.7	n.2643C>T		non_coding_transcript_exon_variant	20/49	5

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108540 AN: 151888 Hom.: 39591 Cov.: 31

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.: 57 AF XY: 0.776 AC XY: 560025 AN XY: 721472

Gnomad4 AFR exome AF: 0.576

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.842

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.766

GnomAD4 genome AF: 0.714 AC: 108591 AN: 152006 Hom.: 39597 Cov.: 31 AF XY: 0.712 AC XY: 52867 AN XY: 74282

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.731

Alfa AF: 0.774 Hom.: 23085

Bravo AF: 0.699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10794288; hg19: chr11-1084821;