rs2120132

Variant names:

• chr10-52766280-T-C
• rs2120132
• NM_001378373.1:c.*1857A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.291
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 300119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378373.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.*1857A>G		3_prime_UTR	Exon 5 of 5	NP_001365302.1	P11226
	MBL2	NM_000242.3		c.*1857A>G		3_prime_UTR	Exon 4 of 4	NP_000233.1	P11226
	MBL2	NM_001378374.1		c.*1857A>G		3_prime_UTR	Exon 5 of 5	NP_001365303.1	P11226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.*1857A>G		3_prime_UTR	Exon 5 of 5	ENSP00000502789.1	P11226
	MBL2	ENST00000373968.3	TSL:1	c.*1857A>G		3_prime_UTR	Exon 4 of 4	ENSP00000363079.3	P11226
	MBL2	ENST00000675947.1		c.*1857A>G		3_prime_UTR	Exon 5 of 5	ENSP00000502615.1	P11226

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.416 AC: 17242 AN: 41430

American (AMR) AF: 0.229 AC: 3501 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3460

East Asian (EAS) AF: 0.172 AC: 890 AN: 5172

South Asian (SAS) AF: 0.200 AC: 965 AN: 4820

European-Finnish (FIN) AF: 0.250 AC: 2644 AN: 10564

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16205 AN: 67952

Other (OTH) AF: 0.279 AC: 588 AN: 2110

Alfa AF: 0.243 Hom.: 6906

Bravo AF: 0.288

Asia WGS AF: 0.206 AC: 720 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mannose-binding lectin deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2120132; hg19: chr10-54526040;