5-177337737-A-G

Position:

• chr5-177337737-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006816.3(LMAN2):​c.482T>C​(p.Leu161Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMAN2 NM_006816.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.24

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.953

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMAN2	NM_006816.3	c.482T>C	p.Leu161Pro	missense_variant	4/8	ENST00000303127.12	NP_006807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN2	ENST00000303127.12	c.482T>C	p.Leu161Pro	missense_variant	4/8	1	NM_006816.3	ENSP00000303366.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.482T>C (p.L161P) alteration is located in exon 4 (coding exon 4) of the LMAN2 gene. This alteration results from a T to C substitution at nucleotide position 482, causing the leucine (L) at amino acid position 161 to be replaced by a proline (P). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.53	D;.;T;.;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D
MetaSVM	Uncertain	0.082	D
MutationAssessor	Uncertain	2.7	M;.;.;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.0	D;D;D;D;D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;.;D;.
Polyphen		1.0	D;D;.;.;.
Vest4		0.89
MutPred		0.86		Loss of stability (P = 0.0045);Loss of stability (P = 0.0045);Loss of stability (P = 0.0045);.;.;
MVP		0.96
MPC		1.4
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.93
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-176764738;