NM_024027.5:c.-26-2664C>G

Variant names:

• chr2-3601651-C-G
• rs12990669
• NM_024027.5:c.-26-2664C>G

Variant summary

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

The NM_024027.5(COLEC11):​c.-26-2664C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,252 control chromosomes in the GnomAD database, including 406 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 0.063 (406 hom., cov: 33)
• Consequence: COLEC11 NM_024027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 3 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC11	NM_024027.5	MANE Select	c.-26-2664C>G		intron	N/A	NP_076932.1
	COLEC11	NM_199235.3		c.-114-2664C>G		intron	N/A	NP_954705.1
	COLEC11	NM_001255982.2		c.-26-2664C>G		intron	N/A	NP_001242911.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC11	ENST00000349077.9	TSL:1 MANE Select	c.-26-2664C>G		intron	N/A	ENSP00000339168.4
	COLEC11	ENST00000236693.11	TSL:1	c.-114-2664C>G		intron	N/A	ENSP00000236693.7
	COLEC11	ENST00000382062.6	TSL:1	c.-26-2664C>G		intron	N/A	ENSP00000371494.2

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9542 AN: 152134 Hom.: 405 Cov.: 33

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.0801

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.0777

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

GnomAD4 genome AF: 0.0626 AC: 9537 AN: 152252 Hom.: 406 Cov.: 33 AF XY: 0.0602 AC XY: 4484 AN XY: 74436

African (AFR) AF: 0.0174 AC: 722 AN: 41572

American (AMR) AF: 0.0623 AC: 952 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 316 AN: 3472

East Asian (EAS) AF: 0.0424 AC: 219 AN: 5164

South Asian (SAS) AF: 0.0804 AC: 388 AN: 4826

European-Finnish (FIN) AF: 0.0386 AC: 409 AN: 10598

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0918 AC: 6246 AN: 68022

Other (OTH) AF: 0.0769 AC: 162 AN: 2106

Alfa AF: 0.0235 Hom.: 23

Bravo AF: 0.0614

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.35
PhyloP100		-0.017
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs12990669; hg19: chr2-3649241;