rs2506

Positions:

• chr10-52765749-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378373.1(MBL2):​c.*2388T>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 0.324 in 151,968 control chromosomes in the GnomAD database, including 9,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9409 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MBL2 NM_001378373.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.87

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP6: Variant 10-52765749-A-C is Benign according to our data. Variant chr10-52765749-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 300109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.*2388T>G		3_prime_UTR_variant	5/5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.*2388T>G		3_prime_UTR_variant	4/4		NP_000233.1
MBL2	NM_001378374.1	c.*2388T>G		3_prime_UTR_variant	5/5		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.*2388T>G		3_prime_UTR_variant	5/5		NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000373968.3	c.*2388T>G		3_prime_UTR_variant	4/4	1		ENSP00000363079	P1
MBL2	ENST00000675947.1	c.*2388T>G		3_prime_UTR_variant	5/5			ENSP00000502615	P1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49086 AN: 151850 Hom.: 9381 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.313

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: 0.324 AC: 49167 AN: 151968 Hom.: 9409 Cov.: 32 AF XY: 0.321 AC XY: 23806 AN XY: 74276

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.311

Alfa AF: 0.254 Hom.: 5036

Bravo AF: 0.336

Asia WGS AF: 0.235 AC: 819 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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	-1.1
CADD	Benign	0.57
DANN	Benign	0.41

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: rs2506; hg19: chr10-54525509;