11-1082921-C-G

Variant names:

• chr11-1082921-C-G
• rs41442048
• NM_002457.5:c.1301C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_002457.5(MUC2):​c.1301C>G​(p.Pro434Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,612,678 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 35)
  • Exomes 𝑓: 0.0046 (25 hom.)
• Consequence: MUC2 NM_002457.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.614
• Publications: 5 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.181).
• BP6: Variant 11-1082921-C-G is Benign according to our data. Variant chr11-1082921-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3024844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.1301C>G	p.Pro434Arg	missense	Exon 10 of 58	NP_002448.5	A0A3S8TMF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC2	ENST00000675028.1		c.1301C>G	p.Pro434Arg	missense	Exon 10 of 30	ENSP00000502432.1	A0A6Q8PGX3
	MUC2	ENST00000361558.7	TSL:5	n.1328C>G		non_coding_transcript_exon	Exon 10 of 49

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 482 AN: 152214 Hom.: 2 Cov.: 35

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00553

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00340 AC: 844 AN: 248154 AF XY: 0.00345

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.000754

Gnomad ASJ exome AF: 0.00130

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.00607

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00458 AC: 6686 AN: 1460346 Hom.: 25 Cov.: 35 AF XY: 0.00451 AC XY: 3274 AN XY: 726426

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 38 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00146 AC: 126 AN: 86258

European-Finnish (FIN) AF: 0.00207 AC: 108 AN: 52112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00548 AC: 6090 AN: 1111820

Other (OTH) AF: 0.00454 AC: 274 AN: 60352

GnomAD4 genome AF: 0.00316 AC: 482 AN: 152332 Hom.: 2 Cov.: 35 AF XY: 0.00301 AC XY: 224 AN XY: 74480

African (AFR) AF: 0.000769 AC: 32 AN: 41586

American (AMR) AF: 0.00105 AC: 16 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00553 AC: 376 AN: 68014

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00155 Hom.: 0

Bravo AF: 0.00274

EpiCase AF: 0.00469

EpiControl AF: 0.00415

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Uncertain	0.99
PhyloP100		0.61
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs41442048; hg19: chr11-1080917;