rs387907075

Variant names:

• chr2-3643807-T-C
• rs387907075
• NM_024027.5:c.505T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_024027.5(COLEC11):​c.505T>C​(p.Ser169Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COLEC11 NM_024027.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.82
• Publications: 9 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-3643807-T-C is Pathogenic according to our data. Variant chr2-3643807-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 30968.Status of the report is no_assertion_criteria_provided, 0 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC11	NM_024027.5	MANE Select	c.505T>C	p.Ser169Pro	missense	Exon 7 of 7	NP_076932.1
	COLEC11	NM_001255985.1		c.547T>C	p.Ser183Pro	missense	Exon 8 of 8	NP_001242914.1
	COLEC11	NM_199235.3		c.496T>C	p.Ser166Pro	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.505T>C	p.Ser169Pro	missense	Exon 7 of 7	ENSP00000339168.4
	COLEC11	ENST00000236693.11	TSL:1	c.496T>C	p.Ser166Pro	missense	Exon 8 of 8	ENSP00000236693.7
	COLEC11	ENST00000382062.6	TSL:1	c.433T>C	p.Ser145Pro	missense	Exon 6 of 6	ENSP00000371494.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250254 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.000198 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	3MC syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Benign	0.20	T
Sift4G	Benign	0.19	T
Polyphen		0.53	P
Vest4		0.51
MutPred		0.62		Gain of catalytic residue at S169 (P = 0.0037)
MVP		0.59
MPC		0.80
ClinPred		0.40	T
GERP RS		1.4
Varity_R		0.94
gMVP		0.85
Mutation Taster		=1/99	disease causing (ClinVar)

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: rs387907075; hg19: chr2-3691397;