rs2083771

Variant names:

• chr10-52765918-T-G
• rs2083771
• NM_001378373.1:c.*2219A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000242.3(MBL2):​c.*2219A>C 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 151,960 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: 33)
  • Failed GnomAD Quality Control
• Consequence: MBL2 NM_000242.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18
• Publications: 8 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=-1.01).
• BP6: Variant 10-52765918-T-G is Benign according to our data. Variant chr10-52765918-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 300110.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000242.3. 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.*2219A>C		3_prime_UTR	Exon 5 of 5	NP_001365302.1
	MBL2	NM_000242.3		c.*2219A>C		3_prime_UTR	Exon 4 of 4	NP_000233.1
	MBL2	NM_001378374.1		c.*2219A>C		3_prime_UTR	Exon 5 of 5	NP_001365303.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.*2219A>C		3_prime_UTR	Exon 5 of 5	ENSP00000502789.1
	MBL2	ENST00000373968.3	TSL:1	c.*2219A>C		3_prime_UTR	Exon 4 of 4	ENSP00000363079.3
	MBL2	ENST00000675947.1		c.*2219A>C		3_prime_UTR	Exon 5 of 5	ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49098 AN: 151842 Hom.: 9381 Cov.: 33

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.314

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: 0.324 AC: 49179 AN: 151960 Hom.: 9409 Cov.: 33 AF XY: 0.321 AC XY: 23832 AN XY: 74284

African (AFR) AF: 0.536 AC: 22197 AN: 41404

American (AMR) AF: 0.265 AC: 4043 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 734 AN: 3454

East Asian (EAS) AF: 0.253 AC: 1310 AN: 5180

South Asian (SAS) AF: 0.204 AC: 981 AN: 4818

European-Finnish (FIN) AF: 0.251 AC: 2652 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16269 AN: 67940

Other (OTH) AF: 0.312 AC: 660 AN: 2116

Alfa AF: 0.263 Hom.: 20587

Bravo AF: 0.336

Asia WGS AF: 0.235 AC: 820 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-1.0
CADD	Benign	0.76
DANN	Benign	0.41
PhyloP100		-1.2
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: rs2083771; hg19: chr10-54525678;