rs11245954

Positions:

• chr11-1107170-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002457.5(MUC2):​c.11497A>G​(p.Ser3833Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,612,550 control chromosomes in the GnomAD database, including 4,681 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.087 (686 hom., cov: 33)
  • Exomes 𝑓: 0.072 (3995 hom.)
• Consequence: MUC2 NM_002457.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC2	NM_002457.5	c.11497A>G	p.Ser3833Gly	missense_variant	50/58	ENST00000713550.1	NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000674892.1	c.1981A>G	p.Ser661Gly	missense_variant	12/20			ENSP00000501871	A2
MUC2	ENST00000361558.7	n.11534A>G		non_coding_transcript_exon_variant	41/49	5

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13237 AN: 152218 Hom.: 685 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0783

GnomAD3 exomes AF: 0.0674 AC: 16715 AN: 247940 Hom.: 663 AF XY: 0.0658 AC XY: 8884 AN XY: 135034

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0370

Gnomad ASJ exome AF: 0.0342

Gnomad EAS exome AF: 0.0542

Gnomad SAS exome AF: 0.0512

Gnomad FIN exome AF: 0.0981

Gnomad NFE exome AF: 0.0699

Gnomad OTH exome AF: 0.0689

GnomAD4 exome AF: 0.0716 AC: 104535 AN: 1460214 Hom.: 3995 Cov.: 32 AF XY: 0.0706 AC XY: 51294 AN XY: 726310

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0402

Gnomad4 ASJ exome AF: 0.0335

Gnomad4 EAS exome AF: 0.0376

Gnomad4 SAS exome AF: 0.0508

Gnomad4 FIN exome AF: 0.0993

Gnomad4 NFE exome AF: 0.0731

Gnomad4 OTH exome AF: 0.0722

GnomAD4 genome AF: 0.0869 AC: 13241 AN: 152336 Hom.: 686 Cov.: 33 AF XY: 0.0856 AC XY: 6374 AN XY: 74502

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0430

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0718 Hom.: 653

Bravo AF: 0.0852

Asia WGS AF: 0.0660 AC: 229 AN: 3478

EpiCase AF: 0.0710

EpiControl AF: 0.0685

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11245954; hg19: chr11-1101078; COSMIC: COSV61244529;