rs10170348

Variant names:

• chr2-3626058-G-A
• rs10170348
• ENST00000236693.11:c.159G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000236693.11(COLEC11):​c.159G>A​(p.Lys53Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,134 control chromosomes in the GnomAD database, including 17,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1276 hom., cov: 33)
  • Exomes 𝑓: 0.14 (16420 hom.)
• Consequence: COLEC11 ENST00000236693.11 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.502
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-3626058-G-A is Benign according to our data. Variant chr2-3626058-G-A is described in ClinVar as Benign. ClinVar VariationId is 402556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.502 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000236693.11. 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.203-11475G>A		intron	N/A	NP_076932.1
	COLEC11	NM_199235.3		c.159G>A	p.Lys53Lys	synonymous	Exon 4 of 8	NP_954705.1
	COLEC11	NM_001255985.1		c.245-11475G>A		intron	N/A	NP_001242914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLEC11	ENST00000236693.11	TSL:1	c.159G>A	p.Lys53Lys	synonymous	Exon 4 of 8	ENSP00000236693.7
	COLEC11	ENST00000349077.9	TSL:1 MANE Select	c.203-11475G>A		intron	N/A	ENSP00000339168.4
	COLEC11	ENST00000382062.6	TSL:1	c.202+12676G>A		intron	N/A	ENSP00000371494.2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16820 AN: 152202 Hom.: 1278 Cov.: 33

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.126 AC: 31634 AN: 251476 AF XY: 0.125

Gnomad AFR exome AF: 0.0332

Gnomad AMR exome AF: 0.0597

Gnomad ASJ exome AF: 0.0869

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.142 AC: 207952 AN: 1460814 Hom.: 16420 Cov.: 32 AF XY: 0.140 AC XY: 101492 AN XY: 726732

African (AFR) AF: 0.0313 AC: 1046 AN: 33470

American (AMR) AF: 0.0618 AC: 2766 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 2304 AN: 26134

East Asian (EAS) AF: 0.309 AC: 12259 AN: 39686

South Asian (SAS) AF: 0.0591 AC: 5097 AN: 86244

European-Finnish (FIN) AF: 0.130 AC: 6926 AN: 53396

Middle Eastern (MID) AF: 0.0758 AC: 437 AN: 5764

European-Non Finnish (NFE) AF: 0.152 AC: 168726 AN: 1111040

Other (OTH) AF: 0.139 AC: 8391 AN: 60356

GnomAD4 genome AF: 0.110 AC: 16819 AN: 152320 Hom.: 1276 Cov.: 33 AF XY: 0.108 AC XY: 8042 AN XY: 74476

African (AFR) AF: 0.0379 AC: 1577 AN: 41582

American (AMR) AF: 0.0833 AC: 1276 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1636 AN: 5172

South Asian (SAS) AF: 0.0621 AC: 300 AN: 4830

European-Finnish (FIN) AF: 0.111 AC: 1179 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10010 AN: 68026

Other (OTH) AF: 0.104 AC: 221 AN: 2116

Alfa AF: 0.130 Hom.: 1880

Bravo AF: 0.108

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		0.50
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: rs10170348; hg19: chr2-3673648; COSMIC: COSV52595850;