11-1082898-C-T

Variant names:

• chr11-1082898-C-T
• rs41453346
• NM_002457.5:c.1278C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_002457.5(MUC2):​c.1278C>T​(p.Tyr426Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,612,590 control chromosomes in the GnomAD database, including 480 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 0.016 (33 hom., cov: 35)
  • Exomes 𝑓: 0.022 (447 hom.)
• Consequence: MUC2 NM_002457.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-3.4 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.016 (2438/152334) while in subpopulation NFE AF = 0.0253 (1723/68018). AF 95% confidence interval is 0.0243. There are 33 homozygotes in GnomAd4. There are 1094 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	NM_002457.5	MANE Select	c.1278C>T	p.Tyr426Tyr	synonymous	Exon 10 of 58	NP_002448.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000675028.1		c.1278C>T	p.Tyr426Tyr	synonymous	Exon 10 of 30	ENSP00000502432.1
	MUC2	ENST00000361558.7	TSL:5	n.1305C>T		non_coding_transcript_exon	Exon 10 of 49

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2437 AN: 152216 Hom.: 33 Cov.: 35

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0148 AC: 3674 AN: 247858 AF XY: 0.0149

Gnomad AFR exome AF: 0.00352

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.00320

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0154

GnomAD4 exome AF: 0.0223 AC: 32618 AN: 1460256 Hom.: 447 Cov.: 35 AF XY: 0.0215 AC XY: 15637 AN XY: 726396

African (AFR) AF: 0.00332 AC: 111 AN: 33480

American (AMR) AF: 0.0113 AC: 507 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00356 AC: 93 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00609 AC: 525 AN: 86256

European-Finnish (FIN) AF: 0.0134 AC: 700 AN: 52076

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5766

European-Non Finnish (NFE) AF: 0.0265 AC: 29467 AN: 1111776

Other (OTH) AF: 0.0197 AC: 1188 AN: 60354

GnomAD4 genome AF: 0.0160 AC: 2438 AN: 152334 Hom.: 33 Cov.: 35 AF XY: 0.0147 AC XY: 1094 AN XY: 74490

African (AFR) AF: 0.00483 AC: 201 AN: 41584

American (AMR) AF: 0.0199 AC: 305 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4828

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0253 AC: 1723 AN: 68018

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0207 Hom.: 15

Bravo AF: 0.0158

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0230

EpiControl AF: 0.0231

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.37
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs41453346; hg19: chr11-1080894;