2-96707303-T-C

Position:

• chr2-96707303-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030805.4(LMAN2L):​c.1000A>G​(p.Ile334Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LMAN2L NM_030805.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62

Genes affected

LMAN2L (HGNC:19263): (lectin, mannose binding 2 like) This gene encodes a protein belonging to the L-type lectin group of type 1 membrane proteins, which function in the mammalian early secretory pathway. These proteins contain luminal carbohydrate recognition domains, which display homology to leguminous lectins. Unlike other proteins of the group, which cycle in the early secretory pathway and are predominantly associated with post endoplasmic reticulum membranes, the protein encoded by this gene is a non-cycling resident protein of the ER, where it functions as a cargo receptor for glycoproteins. It is proposed to regulate exchange of folded proteins for transport to the Golgi and exchange of misfolded glycoproteins for transport to the ubiquitin-proteasome pathway. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085455716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMAN2L	NM_030805.4	c.1000A>G	p.Ile334Val	missense_variant	8/8	ENST00000264963.9	NP_110432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN2L	ENST00000264963.9	c.1000A>G	p.Ile334Val	missense_variant	8/8	1	NM_030805.4	ENSP00000264963.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 21, 2024

The c.1033A>G (p.I345V) alteration is located in exon 9 (coding exon 9) of the LMAN2L gene. This alteration results from a A to G substitution at nucleotide position 1033, causing the isoleucine (I) at amino acid position 345 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.0027
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.52	N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.040	N;N
REVEL	Benign	0.057
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.015	B;B
Vest4		0.13
MutPred		0.27		Gain of ubiquitination at K338 (P = 0.1181);.;
MVP		0.50
MPC		0.19
ClinPred		0.54	D
GERP RS		5.6
Varity_R		0.044
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr2-97373040;