11-1086366-G-A

Variant names:

• chr11-1086366-G-A
• rs11245936
• NM_002457.5:c.2494G>A

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 26 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 -7 ACMG points.

• PP3: Splicing predictors support a deleterious 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.

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.2494G>A	p.Gly832Ser	missense	Exon 19 of 58	NP_002448.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000675028.1		c.2494G>A	p.Gly832Ser	missense	Exon 19 of 30	ENSP00000502432.1
	MUC2	ENST00000361558.7	TSL:5	n.2521G>A		non_coding_transcript_exon	Exon 19 of 49

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

GnomAD2 exomes AF: 0.0706 AC: 17500 AN: 247974 AF XY: 0.0710

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 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

African (AFR) AF: 0.0413 AC: 1383 AN: 33480

American (AMR) AF: 0.0382 AC: 1707 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0448 AC: 1171 AN: 26132

East Asian (EAS) AF: 0.0449 AC: 1783 AN: 39680

South Asian (SAS) AF: 0.0522 AC: 4501 AN: 86252

European-Finnish (FIN) AF: 0.114 AC: 5990 AN: 52684

Middle Eastern (MID) AF: 0.0328 AC: 189 AN: 5766

European-Non Finnish (NFE) AF: 0.0906 AC: 100706 AN: 1111792

Other (OTH) AF: 0.0788 AC: 4756 AN: 60358

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

African (AFR) AF: 0.0396 AC: 1645 AN: 41546

American (AMR) AF: 0.0516 AC: 790 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 140 AN: 3468

East Asian (EAS) AF: 0.0605 AC: 313 AN: 5176

South Asian (SAS) AF: 0.0472 AC: 228 AN: 4832

European-Finnish (FIN) AF: 0.113 AC: 1192 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0897 AC: 6102 AN: 68004

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0792 Hom.: 2069

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
PhyloP100		5.6
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11245936; hg19: chr11-1084362;