Genetic Variant LMAN2:p.Gly222Asp (chr5-177337373-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006816.3(LMAN2):c.665G>A(p.Gly222Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LMAN2
NM_006816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Publications

0 publications found

Variant links:

Genes affected

LMAN2 (HGNC:16986): (lectin, mannose binding 2) This gene encodes a type I transmembrane lectin that shuttles between the endoplasmic reticulum, the Golgi apparatus and the plasma membrane. The encoded protein binds high mannose type glycoproteins and may facilitate their sorting, trafficking and quality control. [provided by RefSeq, Oct 2008]

LMAN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20630428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006816.3. 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
	LMAN2	NM_006816.3	MANE Select	c.665G>A	p.Gly222Asp	missense	Exon 5 of 8	NP_006807.1	Q12907

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LMAN2	ENST00000303127.12	TSL:1 MANE Select	c.665G>A	p.Gly222Asp	missense	Exon 5 of 8	ENSP00000303366.7	Q12907
LMAN2	ENST00000883396.1		c.791G>A	p.Gly264Asp	missense	Exon 6 of 9	ENSP00000553455.1
LMAN2	ENST00000883394.1		c.665G>A	p.Gly222Asp	missense	Exon 5 of 8	ENSP00000553453.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248090

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725932

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111874

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.00032

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.041

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.20

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Benign

0.025

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

PhyloP100

5.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

2.7

REVEL

Uncertain

0.33

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.99

Vest4

0.76

MutPred

0.51

Gain of sheet (P = 0.0149)

MVP

0.66

MPC

1.3

ClinPred

0.79

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.63

Mutation Taster

=57/43

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over