rs2120132

chr10-52766280-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378373.1(MBL2):c.*1857A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,982 control chromosomes in the GnomAD database, including 6,769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6769 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MBL2 NM_001378373.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.291

Genes affected

MBL2 (HGNC:6922): (mannose binding lectin 2) This gene encodes the soluble mannose-binding lectin or mannose-binding protein found in serum. The protein encoded belongs to the collectin family and is an important element in the innate immune system. The protein recognizes and binds to mannose and N-acetylglucosamine on many microorganisms, including bacteria, yeast, and viruses including influenza virus, HIV and SARS-CoV. This binding activates the classical complement pathway. Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases. [provided by RefSeq, Jun 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 10-52766280-T-C is Benign according to our data. Variant chr10-52766280-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 300119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBL2	NM_001378373.1	c.*1857A>G		3_prime_UTR_variant	5/5	ENST00000674931.1
MBL2	NM_000242.3	c.*1857A>G		3_prime_UTR_variant	4/4
MBL2	NM_001378374.1	c.*1857A>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBL2	ENST00000674931.1	c.*1857A>G		3_prime_UTR_variant	5/5		NM_001378373.1	P1
MBL2	ENST00000373968.3	c.*1857A>G		3_prime_UTR_variant	4/4	1		P1
MBL2	ENST00000675947.1	c.*1857A>G		3_prime_UTR_variant	5/5			P1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43022 AN: 151866 Hom.: 6755 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.280

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.283 AC: 43078 AN: 151982 Hom.: 6769 Cov.: 32 AF XY: 0.281 AC XY: 20881 AN XY: 74270

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.279

Alfa AF: 0.240 Hom.: 5617

Bravo AF: 0.288

Asia WGS AF: 0.206 AC: 720 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mannose-binding lectin deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.5
Dann	Benign	0.69

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: rs2120132; hg19: chr10-54526040;