2-3643958-A-G

Variant names:

• chr2-3643958-A-G
• rs7567833
• NM_024027.5:c.656A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024027.5(COLEC11):​c.656A>G​(p.His219Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0685 in 1,613,746 control chromosomes in the GnomAD database, including 19,382 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (9520 hom., cov: 34)
  • Exomes 𝑓: 0.053 (9862 hom.)
• Consequence: COLEC11 NM_024027.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.72
• Publications: 31 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.5731377E-6).
• BP6: Variant 2-3643958-A-G is Benign according to our data. Variant chr2-3643958-A-G is described in ClinVar as Benign. ClinVar VariationId is 1588878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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.656A>G	p.His219Arg	missense	Exon 7 of 7	NP_076932.1
	COLEC11	NM_001255985.1		c.698A>G	p.His233Arg	missense	Exon 8 of 8	NP_001242914.1
	COLEC11	NM_199235.3		c.647A>G	p.His216Arg	missense	Exon 8 of 8	NP_954705.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC11	ENST00000349077.9	TSL:1 MANE Select	c.656A>G	p.His219Arg	missense	Exon 7 of 7	ENSP00000339168.4
	COLEC11	ENST00000236693.11	TSL:1	c.647A>G	p.His216Arg	missense	Exon 8 of 8	ENSP00000236693.7
	COLEC11	ENST00000382062.6	TSL:1	c.584A>G	p.His195Arg	missense	Exon 6 of 6	ENSP00000371494.2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32710 AN: 151850 Hom.: 9482 Cov.: 34

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0213

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.0845 AC: 21235 AN: 251312 AF XY: 0.0749

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.0485

Gnomad ASJ exome AF: 0.0367

Gnomad EAS exome AF: 0.0171

Gnomad FIN exome AF: 0.0186

Gnomad NFE exome AF: 0.0339

Gnomad OTH exome AF: 0.0592

GnomAD4 exome AF: 0.0531 AC: 77681 AN: 1461780 Hom.: 9862 Cov.: 32 AF XY: 0.0528 AC XY: 38427 AN XY: 727196

African (AFR) AF: 0.692 AC: 23166 AN: 33478

American (AMR) AF: 0.0540 AC: 2413 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 980 AN: 26136

East Asian (EAS) AF: 0.0181 AC: 719 AN: 39700

South Asian (SAS) AF: 0.104 AC: 8953 AN: 86258

European-Finnish (FIN) AF: 0.0193 AC: 1027 AN: 53324

Middle Eastern (MID) AF: 0.121 AC: 698 AN: 5768

European-Non Finnish (NFE) AF: 0.0313 AC: 34829 AN: 1111996

Other (OTH) AF: 0.0811 AC: 4896 AN: 60396

GnomAD4 genome AF: 0.216 AC: 32804 AN: 151966 Hom.: 9520 Cov.: 34 AF XY: 0.210 AC XY: 15594 AN XY: 74258

African (AFR) AF: 0.667 AC: 27684 AN: 41488

American (AMR) AF: 0.0921 AC: 1405 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3468

East Asian (EAS) AF: 0.0214 AC: 110 AN: 5142

South Asian (SAS) AF: 0.110 AC: 528 AN: 4804

European-Finnish (FIN) AF: 0.0167 AC: 176 AN: 10550

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0336 AC: 2284 AN: 67936

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.0868 Hom.: 12019

Bravo AF: 0.239

TwinsUK AF: 0.0324 AC: 120

ALSPAC AF: 0.0304 AC: 117

ESP6500AA AF: 0.660 AC: 2910

ESP6500EA AF: 0.0324 AC: 279

ExAC AF: 0.0987 AC: 11983

Asia WGS AF: 0.107 AC: 376 AN: 3478

EpiCase AF: 0.0351

EpiControl AF: 0.0359

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0000076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.89	N
PhyloP100		4.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.14
Sift	Benign	0.48	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.11
MPC		0.47
ClinPred		0.0040	T
GERP RS		5.3
Varity_R		0.25
gMVP		0.54
Mutation Taster		=99/1	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: rs7567833; hg19: chr2-3691548; COSMIC: COSV52593465; COSMIC: COSV52593465;