2-3604363-T-C

Position:

• chr2-3604363-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024027.5(COLEC11):​c.23T>C​(p.Val8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,614,254 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00082 (19 hom.)
• Consequence: COLEC11 NM_024027.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0200

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005987972).
• BP6: Variant 2-3604363-T-C is Benign according to our data. Variant chr2-3604363-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00691 (1053/152364) while in subpopulation AFR AF= 0.0237 (985/41584). AF 95% confidence interval is 0.0225. There are 9 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLEC11	NM_024027.5	c.23T>C	p.Val8Ala	missense_variant	2/7	ENST00000349077.9	NP_076932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLEC11	ENST00000349077.9	c.23T>C	p.Val8Ala	missense_variant	2/7	1	NM_024027.5	ENSP00000339168	P1

Frequencies

GnomAD3 genomes AF: 0.00684 AC: 1041 AN: 152246 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00184 AC: 462 AN: 251458 Hom.: 2 AF XY: 0.00134 AC XY: 182 AN XY: 135904

Gnomad AFR exome AF: 0.0250

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000817 AC: 1194 AN: 1461890 Hom.: 19 Cov.: 31 AF XY: 0.000710 AC XY: 516 AN XY: 727248

Gnomad4 AFR exome AF: 0.0273

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00189

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00691 AC: 1053 AN: 152364 Hom.: 9 Cov.: 33 AF XY: 0.00636 AC XY: 474 AN XY: 74518

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00149 Hom.: 4

Bravo AF: 0.00808

ESP6500AA AF: 0.0227 AC: 100

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00231 AC: 280

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 19, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	0.042
DANN	Benign	0.39
DEOGEN2	Benign	0.017	.;T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.29	T;T;T;T
MetaRNN	Benign	0.0060	T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.90	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.080	N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.13
MVP		0.13
MPC		0.47
ClinPred		0.0022	T
GERP RS		-4.9
Varity_R		0.021
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs113269917; hg19: chr2-3651953;