2-3613345-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The ENST00000236693.11(COLEC11):c.77C>T(p.Pro26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000646 in 1,609,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (1 hom.)
• Consequence: COLEC11 ENST00000236693.11 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.492

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 -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034228355).
• BP6: Variant 2-3613345-C-T is Benign according to our data. Variant chr2-3613345-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-3613345-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLEC11	NM_024027.5	c.165C>T	p.Pro55=	synonymous_variant	3/7	ENST00000349077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLEC11	ENST00000349077.9	c.165C>T	p.Pro55=	synonymous_variant	3/7	1	NM_024027.5	P1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000360 AC: 86 AN: 238578 Hom.: 0 AF XY: 0.000341 AC XY: 44 AN XY: 129084

Gnomad AFR exome AF: 0.0000664

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000341

Gnomad FIN exome AF: 0.000152

Gnomad NFE exome AF: 0.000679

Gnomad OTH exome AF: 0.000516

GnomAD4 exome AF: 0.000664 AC: 968 AN: 1457418 Hom.: 1 Cov.: 32 AF XY: 0.000640 AC XY: 464 AN XY: 724446

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.000377

Gnomad4 NFE exome AF: 0.000827

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74336

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000821 Hom.: 0

Bravo AF: 0.000499

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000297 AC: 36

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	7.1
Dann	Benign	0.95
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;N
PROVEAN	Benign	0.34	N
REVEL	Benign	0.095
Sift	Benign	0.31	T
Sift4G	Uncertain	0.041	D
Polyphen		0.13	B
Vest4		0.30
MVP		0.21
ClinPred		0.032	T
GERP RS		-0.91

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: rs62107197; hg19: chr2-3660935;