rs10824792

Positions:

• chr10-52766446-C-T

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.*1691G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,818 control chromosomes in the GnomAD database, including 20,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (20132 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MBL2 NM_001378373.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.460

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=-0.9).
• BP6: Variant 10-52766446-C-T is Benign according to our data. Variant chr10-52766446-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 300124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.*1691G>A		3_prime_UTR_variant	5/5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.*1691G>A		3_prime_UTR_variant	4/4		NP_000233.1
MBL2	NM_001378374.1	c.*1691G>A		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.*1691G>A		3_prime_UTR_variant	5/5		NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000373968.3	c.*1691G>A		3_prime_UTR_variant	4/4	1		ENSP00000363079	P1
MBL2	ENST00000675947.1	c.*1691G>A		3_prime_UTR_variant	5/5			ENSP00000502615	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73424 AN: 151698 Hom.: 20124 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.484 AC: 73446 AN: 151816 Hom.: 20132 Cov.: 31 AF XY: 0.489 AC XY: 36282 AN XY: 74220

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.496

Alfa AF: 0.578 Hom.: 49038

Bravo AF: 0.475

Asia WGS AF: 0.574 AC: 1992 AN: 3476

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	-0.90
CADD	Benign	0.81
DANN	Benign	0.62

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: rs10824792; hg19: chr10-54526206;