NM_024027.5:c.82_94delGCTGGCGATGACG

Variant names:

• chr2-3604419-CCGGCTGGCGATGA-C
• NM_024027.5:c.82_94delGCTGGCGATGACG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PP5_Moderate

The NM_024027.5(COLEC11):​c.82_94delGCTGGCGATGACG​(p.Ala28ProfsTer69) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COLEC11 NM_024027.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.07
• Publications: 0 publications found

Genes affected

COLEC11 (HGNC:17213): (collectin subfamily member 11) This gene encodes a member of the collectin family of C-type lectins that possess collagen-like sequences and carbohydrate recognition domains. Collectins are secreted proteins that play important roles in the innate immune system by binding to carbohydrate antigens on microorganisms, facilitating their recognition and removal. The encoded protein binds to multiple sugars with a preference for fucose and mannose. Mutations in this gene are a cause of 3MC syndrome-2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

COLEC11 Gene-Disease associations (from GenCC):

• 3MC syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000237370 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
• PP5: Variant 2-3604419-CCGGCTGGCGATGA-C is Pathogenic according to our data. Variant chr2-3604419-CCGGCTGGCGATGA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 3068586.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024027.5. 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
	COLEC11	NM_024027.5	MANE Select	c.82_94delGCTGGCGATGACG	p.Ala28ProfsTer69	frameshift	Exon 2 of 7	NP_076932.1	Q9BWP8-1
	COLEC11	NM_001255985.1		c.124_136delGCTGGCGATGACG	p.Ala42ProfsTer69	frameshift	Exon 3 of 8	NP_001242914.1	Q9BWP8-10
	COLEC11	NM_001255982.2		c.82_94delGCTGGCGATGACG	p.Ala28ProfsTer45	frameshift	Exon 2 of 6	NP_001242911.1	Q9BWP8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC11	ENST00000349077.9	TSL:1 MANE Select	c.82_94delGCTGGCGATGACG	p.Ala28ProfsTer69	frameshift	Exon 2 of 7	ENSP00000339168.4	Q9BWP8-1
	COLEC11	ENST00000382062.6	TSL:1	c.82_94delGCTGGCGATGACG	p.Ala28ProfsTer45	frameshift	Exon 2 of 6	ENSP00000371494.2	Q9BWP8-3
	COLEC11	ENST00000236693.11	TSL:1	c.-7_6delGCTGGCGATGACG	p.Met1fs	frameshift start_lost	Exon 2 of 8	ENSP00000236693.7	Q9BWP8-9

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	3MC syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

Splicing

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

Other links and lift over

hg19: chr2-3652009;