2-3606254-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -1.20

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 -14 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_single_submitter, 1 stars. Variant chr2-3606254-T-C is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
COLEC11	NM_024027.5	c.130+1784T>C		intron_variant		ENST00000349077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLEC11	ENST00000349077.9	c.130+1784T>C		intron_variant		1	NM_024027.5	P1

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

GnomAD3 exomes AF: 0.753 AC: 110397 AN: 146552 Hom.: 42301 AF XY: 0.758 AC XY: 59903 AN XY: 79032

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 SAS exome AF: 0.884

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

Gnomad4 AFR exome AF: 0.608

Gnomad4 AMR exome AF: 0.831

Gnomad4 ASJ exome AF: 0.608

Gnomad4 EAS exome AF: 0.844

Gnomad4 SAS exome AF: 0.884

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.700

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

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.711

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.0
Dann	Benign	0.22

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

LitVar

Other links and lift over

dbSNP: rs3739147; hg19: chr2-3653844;