11-1100449-A-G

Variant names:

• chr11-1100449-A-G
• rs10902089
• NM_002457.5:c.9773-308A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002457.5(MUC2):​c.9773-308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,116 control chromosomes in the GnomAD database, including 22,094 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 0.52 (22094 hom., cov: 33)
• Consequence: MUC2 NM_002457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.36
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	NM_002457.5	MANE Select	c.9773-308A>G		intron	N/A	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000674892.1		c.257-308A>G		intron	N/A	ENSP00000501871.1	A0A6Q8PFN2
	MUC2	ENST00000361558.7	TSL:5	n.9810-308A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79203 AN: 151998 Hom.: 22071 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.0687

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.521 AC: 79273 AN: 152116 Hom.: 22094 Cov.: 33 AF XY: 0.514 AC XY: 38192 AN XY: 74344

African (AFR) AF: 0.684 AC: 28421 AN: 41528

American (AMR) AF: 0.399 AC: 6100 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.0691 AC: 358 AN: 5182

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4816

European-Finnish (FIN) AF: 0.532 AC: 5629 AN: 10572

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34306 AN: 67954

Other (OTH) AF: 0.478 AC: 1009 AN: 2112

Alfa AF: 0.496 Hom.: 18196

Bravo AF: 0.517

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
PhyloP100		-5.4

Splicing

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

Other links and lift over

dbSNP: rs10902089; hg19: chr11-1094357;