rs11245936

chr11-1086366-G-Achr11-1086366-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3 BA1

The NM_002457.5(MUC2):c.2494G>A(p.Gly832Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0823 in 1,613,088 control chromosomes in the GnomAD database, including 5,881 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.070 (413 hom., cov: 33)
  • Exomes 𝑓: 0.084 (5468 hom.)
• Consequence: MUC2 NM_002457.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59

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 -7 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC2	NM_002457.5	c.2494G>A	p.Gly832Ser	missense_variant	19/58	ENST00000713550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC2	ENST00000675028.1	c.2494G>A	p.Gly832Ser	missense_variant	19/30			P3
MUC2	ENST00000361558.7	n.2521G>A		non_coding_transcript_exon_variant	19/49	5

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10593 AN: 152124 Hom.: 413 Cov.: 33

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.0452

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.0664

GnomAD3 exomes AF: 0.0706 AC: 17500 AN: 247974 Hom.: 706 AF XY: 0.0710 AC XY: 9578 AN XY: 134982

Gnomad AFR exome AF: 0.0403

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.0454

Gnomad EAS exome AF: 0.0641

Gnomad SAS exome AF: 0.0517

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0856

Gnomad OTH exome AF: 0.0722

GnomAD4 exome AF: 0.0836 AC: 122186 AN: 1460846 Hom.: 5468 Cov.: 34 AF XY: 0.0828 AC XY: 60154 AN XY: 726688

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.0382

Gnomad4 ASJ exome AF: 0.0448

Gnomad4 EAS exome AF: 0.0449

Gnomad4 SAS exome AF: 0.0522

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0906

Gnomad4 OTH exome AF: 0.0788

GnomAD4 genome AF: 0.0696 AC: 10596 AN: 152242 Hom.: 413 Cov.: 33 AF XY: 0.0695 AC XY: 5173 AN XY: 74422

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.0605

Gnomad4 SAS AF: 0.0472

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0897

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0797 Hom.: 1069

Bravo AF: 0.0640

Asia WGS AF: 0.0600 AC: 208 AN: 3478

EpiCase AF: 0.0857

EpiControl AF: 0.0804

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.040
Cadd	Uncertain	24
Dann	Uncertain	0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.66		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.66		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11245936; hg19: chr11-1084362;