dbSNP rs779142171: COLEC11:p.Gly9Asp (chr2-3604366-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024027.5(COLEC11):c.26G>A(p.Gly9Asp) 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 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G9V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COLEC11
NM_024027.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.876

Publications

0 publications found

Variant links:

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

COLEC11 links:

ENSG00000237370 (HGNC:):

ENSG00000237370 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC11	NM_024027.5 link	c.26G>A	p.Gly9Asp	missense_variant	Exon 2 of 7	ENST00000349077.9	NP_076932.1	Q9BWP8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC11	ENST00000349077.9 link	c.26G>A	p.Gly9Asp	missense_variant	Exon 2 of 7	1	NM_024027.5	ENSP00000339168.4		Q9BWP8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.033

.;T;.;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.64

T;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.79

D;D;D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

1.2

L;L;.;.

PhyloP100

0.88

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.57

P;B;.;.

Vest4

0.34

MutPred

0.70

Gain of solvent accessibility (P = 0.0149);Gain of solvent accessibility (P = 0.0149);.;.;

MVP

0.68

MPC

0.99

ClinPred

0.13

GERP RS

2.5

Varity_R

0.096

gMVP

0.45

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over