11-1102586-C-T

Variant names:

• chr11-1102586-C-T
• rs6421972
• NM_002457.5:c.10539C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002457.5(MUC2):​c.10539C>T​(p.Cys3513Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,612,546 control chromosomes in the GnomAD database, including 123,324 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 0.30 (8394 hom., cov: 34)
  • Exomes 𝑓: 0.38 (114930 hom.)
• Consequence: MUC2 NM_002457.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC2	NM_002457.5	c.10539C>T	p.Cys3513Cys	synonymous_variant	Exon 43 of 58		NP_002448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC2	ENST00000674892.1	c.1023C>T	p.Cys341Cys	synonymous_variant	Exon 5 of 20			ENSP00000501871.1
MUC2	ENST00000361558.7	n.10576C>T		non_coding_transcript_exon_variant	Exon 34 of 49	5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45623 AN: 152150 Hom.: 8391 Cov.: 34

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.385 AC: 562190 AN: 1460278 Hom.: 114930 Cov.: 70 AF XY: 0.381 AC XY: 276933 AN XY: 726416

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.00479

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.300 AC: 45645 AN: 152268 Hom.: 8394 Cov.: 34 AF XY: 0.299 AC XY: 22283 AN XY: 74456

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.304

Alfa AF: 0.386 Hom.: 19613

Bravo AF: 0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	7.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6421972; hg19: chr11-1096494;