6-33776996-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181336.4(LEMD2):​c.1319G>C​(p.Gly440Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

LEMD2
NM_181336.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92
Variant links:
Genes affected
LEMD2 (HGNC:21244): (LEM domain nuclear envelope protein 2) This gene encodes a LEM domain-containing transmembrane protein of the inner nuclear membrane. The protein is involved in nuclear structure organization and plays a role in cell signaling and differentiation. Mutations in this gene result in Cataract 46, juvenile-onset. Multiple transcript variants have been found for this gene. [provided by RefSeq, Feb 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.288817).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LEMD2NM_181336.4 linkc.1319G>C p.Gly440Ala missense_variant 8/9 ENST00000293760.10 NP_851853.1
LEMD2NM_001348710.2 linkc.920G>C p.Gly307Ala missense_variant 8/9 NP_001335639.1
LEMD2NM_001143944.1 linkc.413G>C p.Gly138Ala missense_variant 7/8 NP_001137416.1
LEMD2NM_001348709.2 linkc.413G>C p.Gly138Ala missense_variant 8/9 NP_001335638.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LEMD2ENST00000293760.10 linkc.1319G>C p.Gly440Ala missense_variant 8/91 NM_181336.4 ENSP00000293760.5 Q8NC56-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 20, 2024The c.1319G>C (p.G440A) alteration is located in exon 8 (coding exon 8) of the LEMD2 gene. This alteration results from a G to C substitution at nucleotide position 1319, causing the glycine (G) at amino acid position 440 to be replaced by an alanine (A). 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
0.84
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;T;T;.
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.94
D;.;D;D
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.29
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;M;M;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
0.020
N;N;.;N
REVEL
Benign
0.23
Sift
Benign
0.95
T;T;.;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
1.0
.;D;D;.
Vest4
0.50, 0.50, 0.51
MutPred
0.46
.;Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);.;
MVP
0.55
MPC
1.5
ClinPred
0.69
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.087
gMVP
0.86

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.

Other links and lift over

dbSNP: rs1767444862; hg19: chr6-33744773; API