Genetic Variant NM_006816.3:c.813G>T (chr5-177334381-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006816.3(LMAN2):c.813G>T(p.Met271Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LMAN2
NM_006816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMAN2	NM_006816.3 link	c.813G>T	p.Met271Ile	missense_variant	Exon 7 of 8	ENST00000303127.12	NP_006807.1	Q12907A0A384NPY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN2	ENST00000303127.12 link	c.813G>T	p.Met271Ile	missense_variant	Exon 7 of 8	1	NM_006816.3	ENSP00000303366.7		Q12907

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250730

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461140

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.813G>T (p.M271I) alteration is located in exon 7 (coding exon 7) of the LMAN2 gene. This alteration results from a G to T substitution at nucleotide position 813, causing the methionine (M) at amino acid position 271 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.064

T;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.073

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.95

N;N;N

REVEL

Benign

0.070

Sift

Benign

0.76

T;T;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.32

MutPred

0.48

Gain of methylation at K272 (P = 0.0444);Gain of methylation at K272 (P = 0.0444);.;

MVP

0.55

MPC

0.38

ClinPred

0.20

GERP RS

3.6

Varity_R

0.12

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -4

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over