2-3604419-CCGGCTGGCGATGA-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_024027.5(COLEC11):c.82_94del(p.Ala28ProfsTer69) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. 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

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 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 10 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-3604419-CCGGCTGGCGATGA-C is Pathogenic according to our data. Variant chr2-3604419-CCGGCTGGCGATGA-C is described in ClinVar as [Pathogenic]. Clinvar id is 3068586.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLEC11	NM_024027.5	c.82_94del	p.Ala28ProfsTer69	frameshift_variant	2/7	ENST00000349077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLEC11	ENST00000349077.9	c.82_94del	p.Ala28ProfsTer69	frameshift_variant	2/7	1	NM_024027.5	P1

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

3MC syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

Jul 07, 2023

This sequence change in COLEC11 is a frameshift variant predicted to cause a premature stop codon, p.(Ala28Profs*69), in biologically relevant exon 5/7 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. This variant is absent from the population database gnomAD v2.1 and v3.1. This variant has been detected homozygous in at least one individual with 3MC syndrome (Kulak et al, https://motto.tc/siteler/www.cocukgenetik2019.com/cocuk-genetik-bildiri-kitabi.pdf). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting, PM3_Supporting. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-3652009;