2-3606254-T-C

Variant names:

• chr2-3606254-T-C
• rs3739147
• NM_024027.5:c.130+1784T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024027.5(COLEC11):​c.130+1784T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,548,874 control chromosomes in the GnomAD database, including 382,192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36456 hom., cov: 31)
  • Exomes 𝑓: 0.70 (345736 hom.)
• Consequence: COLEC11 NM_024027.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 2-3606254-T-C is Benign according to our data. Variant chr2-3606254-T-C is described in ClinVar as [Benign]. Clinvar id is 402557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC11	NM_024027.5	c.130+1784T>C		intron_variant	Intron 2 of 6	ENST00000349077.9	NP_076932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC11	ENST00000349077.9	c.130+1784T>C		intron_variant	Intron 2 of 6	1	NM_024027.5	ENSP00000339168.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104553 AN: 151894 Hom.: 36423 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.753 AC: 110397 AN: 146552 AF XY: 0.758

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.841

Gnomad ASJ exome AF: 0.609

Gnomad EAS exome AF: 0.844

Gnomad FIN exome AF: 0.771

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.701 AC: 978659 AN: 1396862 Hom.: 345736 Cov.: 37 AF XY: 0.706 AC XY: 486736 AN XY: 689028

African (AFR) AF: 0.608 AC: 19187 AN: 31566

American (AMR) AF: 0.831 AC: 29657 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15309 AN: 25166

East Asian (EAS) AF: 0.844 AC: 30148 AN: 35728

South Asian (SAS) AF: 0.884 AC: 69997 AN: 79206

European-Finnish (FIN) AF: 0.757 AC: 36442 AN: 48116

Middle Eastern (MID) AF: 0.710 AC: 4047 AN: 5696

European-Non Finnish (NFE) AF: 0.680 AC: 733291 AN: 1077728

Other (OTH) AF: 0.700 AC: 40581 AN: 57954

GnomAD4 genome AF: 0.688 AC: 104644 AN: 152012 Hom.: 36456 Cov.: 31 AF XY: 0.701 AC XY: 52093 AN XY: 74282

African (AFR) AF: 0.611 AC: 25312 AN: 41448

American (AMR) AF: 0.760 AC: 11605 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2142 AN: 3470

East Asian (EAS) AF: 0.848 AC: 4365 AN: 5148

South Asian (SAS) AF: 0.882 AC: 4251 AN: 4822

European-Finnish (FIN) AF: 0.773 AC: 8169 AN: 10568

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46599 AN: 67970

Other (OTH) AF: 0.711 AC: 1503 AN: 2114

Alfa AF: 0.630 Hom.: 3727

Bravo AF: 0.680

Asia WGS AF: 0.825 AC: 2868 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.0
DANN	Benign	0.22
PhyloP100		-1.2
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3739147; hg19: chr2-3653844;