NM_002457.5:c.1000+26T>C

Variant names:

• chr11-1081813-T-C
• rs10902081
• NM_002457.5:c.1000+26T>C

Variant summary

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

The NM_002457.5(MUC2):​c.1000+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,538,258 control chromosomes in the GnomAD database, including 243,008 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 0.61 (29367 hom., cov: 34)
  • Exomes 𝑓: 0.55 (213641 hom.)
• Consequence: MUC2 NM_002457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 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.1000+26T>C		intron	N/A	NP_002448.5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000675028.1		c.1000+26T>C		intron	N/A	ENSP00000502432.1
	MUC2	ENST00000361558.7	TSL:5	n.1027+26T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92948 AN: 152034 Hom.: 29325 Cov.: 34

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.550 AC: 761901 AN: 1386106 Hom.: 213641 Cov.: 47 AF XY: 0.552 AC XY: 375547 AN XY: 680214

African (AFR) AF: 0.743 AC: 23454 AN: 31552

American (AMR) AF: 0.750 AC: 27021 AN: 36012

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 12721 AN: 25034

East Asian (EAS) AF: 0.800 AC: 28475 AN: 35606

South Asian (SAS) AF: 0.684 AC: 54129 AN: 79154

European-Finnish (FIN) AF: 0.537 AC: 25231 AN: 46972

Middle Eastern (MID) AF: 0.534 AC: 2947 AN: 5514

European-Non Finnish (NFE) AF: 0.520 AC: 555459 AN: 1068946

Other (OTH) AF: 0.566 AC: 32464 AN: 57316

GnomAD4 genome AF: 0.612 AC: 93050 AN: 152152 Hom.: 29367 Cov.: 34 AF XY: 0.615 AC XY: 45771 AN XY: 74374

African (AFR) AF: 0.738 AC: 30649 AN: 41524

American (AMR) AF: 0.687 AC: 10521 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3470

East Asian (EAS) AF: 0.833 AC: 4306 AN: 5168

South Asian (SAS) AF: 0.686 AC: 3313 AN: 4828

European-Finnish (FIN) AF: 0.540 AC: 5723 AN: 10592

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35000 AN: 67950

Other (OTH) AF: 0.585 AC: 1236 AN: 2112

Alfa AF: 0.486 Hom.: 3026

Bravo AF: 0.630

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10902081; hg19: chr11-1079809;