Variant 10-52771482-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_001378373.1(MBL2):c.154C>A(p.Arg52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MBL2
NM_001378373.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.972

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr10-52771482-G-A is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.28390634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MBL2	NM_001378373.1 linkuse as main transcript	c.154C>A	p.Arg52Ser	missense_variant	2/5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3 linkuse as main transcript	c.154C>A	p.Arg52Ser	missense_variant	1/4		NP_000233.1
MBL2	NM_001378374.1 linkuse as main transcript	c.154C>A	p.Arg52Ser	missense_variant	2/5		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MBL2	ENST00000674931.1 linkuse as main transcript	c.154C>A	p.Arg52Ser	missense_variant	2/5		NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000373968.3 linkuse as main transcript	c.154C>A	p.Arg52Ser	missense_variant	1/4	1		ENSP00000363079	P1
MBL2	ENST00000675947.1 linkuse as main transcript	c.154C>A	p.Arg52Ser	missense_variant	2/5			ENSP00000502615	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.078

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.057

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.039

MetaRNN

Benign

0.28

MetaSVM

Uncertain

0.54

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.66

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.29

Sift

Benign

0.033

Sift4G

Benign

0.065

Polyphen

0.57

Vest4

0.12

MutPred

0.34

Gain of phosphorylation at R52 (P = 0.0196);

MVP

0.93

MPC

0.34

ClinPred

0.92

GERP RS

3.1

Varity_R

0.30

gMVP

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over