2-3604350-A-C

Position:

• chr2-3604350-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024027.5(COLEC11):​c.10A>C​(p.Asn4His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COLEC11 NM_024027.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13757792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLEC11	NM_024027.5	c.10A>C	p.Asn4His	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.10A>C	p.Asn4His	missense_variant	2/7	1	NM_024027.5	ENSP00000339168	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.10A>C (p.N4H) alteration is located in exon 2 (coding exon 1) of the COLEC11 gene. This alteration results from a A to C substitution at nucleotide position 10, causing the asparagine (N) at amino acid position 4 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	1.1
DANN	Benign	0.61
DEOGEN2	Benign	0.012	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.32	T;T;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.34	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.87	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.23
MutPred		0.41		Loss of catalytic residue at N4 (P = 0.0045);Loss of catalytic residue at N4 (P = 0.0045);.;.;
MVP		0.66
MPC		0.40
ClinPred		0.098	T
GERP RS		0.92
Varity_R		0.049
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1299334460; hg19: chr2-3651940;