dbSNP rs2120131: MBL2:c.*1879A>C (chr10-52766258-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378373.1(MBL2):c.*1879A>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 0.284 in 151,942 control chromosomes in the GnomAD database, including 6,780 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 ( 6780 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

MBL2
NM_001378373.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.985

Publications

13 publications found

Variant links:

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]

MBL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 10-52766258-T-G is Benign according to our data. Variant chr10-52766258-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 300118.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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBL2	NM_001378373.1	MANE Select	c.*1879A>C	3_prime_UTR	Exon 5 of 5	NP_001365302.1	P11226
MBL2	NM_000242.3		c.*1879A>C	3_prime_UTR	Exon 4 of 4	NP_000233.1	P11226
MBL2	NM_001378374.1		c.*1879A>C	3_prime_UTR	Exon 5 of 5	NP_001365303.1	P11226

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MBL2	ENST00000674931.1	MANE Select	c.*1879A>C	3_prime_UTR	Exon 5 of 5	ENSP00000502789.1	P11226
MBL2	ENST00000373968.3	TSL:1	c.*1879A>C	3_prime_UTR	Exon 4 of 4	ENSP00000363079.3	P11226
MBL2	ENST00000675947.1		c.*1879A>C	3_prime_UTR	Exon 5 of 5	ENSP00000502615.1	P11226

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43046

AN:

151824

Hom.:

6766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.281

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.284

AC:

43102

AN:

151942

Hom.:

6780

Cov.:

AF XY:

0.282

AC XY:

20906

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.416

AC:

17249

AN:

41424

American (AMR)

AF:

0.229

AC:

3501

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

713

AN:

3458

East Asian (EAS)

AF:

0.172

AC:

889

AN:

5174

South Asian (SAS)

AF:

0.201

AC:

968

AN:

4822

European-Finnish (FIN)

AF:

0.250

AC:

2641

AN:

10550

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.239

AC:

16224

AN:

67946

Other (OTH)

AF:

0.279

AC:

590

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1560

3120

4680

6240

7800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.254

Hom.:

11218

Bravo

AF:

0.288

Asia WGS

AF:

0.207

AC:

721

AN:

3474

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mannose-binding lectin deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.7

(source)

DANN

Benign

0.90

PhyloP100

-0.98

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over