rs758745859

Variant names:

• chr2-3604451-C-A
• rs758745859
• ENST00000236693.11:c.23C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-3604451-C-A
• chr2-3604451-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199235.3(COLEC11):​c.23C>A​(p.Ser8Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COLEC11 NM_199235.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06243807).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199235.3. 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.111C>A	p.Ile37Ile	synonymous	Exon 2 of 7	NP_076932.1	Q9BWP8-1
	COLEC11	NM_199235.3		c.23C>A	p.Ser8Tyr	missense	Exon 2 of 8	NP_954705.1	Q9BWP8-9
	COLEC11	NM_001255985.1		c.153C>A	p.Ile51Ile	synonymous	Exon 3 of 8	NP_001242914.1	Q9BWP8-10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC11	ENST00000236693.11	TSL:1	c.23C>A	p.Ser8Tyr	missense	Exon 2 of 8	ENSP00000236693.7	Q9BWP8-9
	COLEC11	ENST00000349077.9	TSL:1 MANE Select	c.111C>A	p.Ile37Ile	synonymous	Exon 2 of 7	ENSP00000339168.4	Q9BWP8-1
	COLEC11	ENST00000382062.6	TSL:1	c.111C>A	p.Ile37Ile	synonymous	Exon 2 of 6	ENSP00000371494.2	Q9BWP8-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.2
DANN	Benign	0.85
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.73
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.037
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.33
MutPred		0.28		Gain of solvent accessibility (P = 0.0739)
MVP		0.16
ClinPred		0.14	T
GERP RS		-7.0
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs758745859; hg19: chr2-3652041;