chr6-33789079-A-C
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_181336.4(LEMD2):c.38T>G(p.Leu13Arg) variant causes a missense change involving the alteration of a non-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 Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
LEMD2
NM_181336.4 missense
NM_181336.4 missense
Scores
10
5
3
Clinical Significance
Conservation
PhyloP100: 2.81
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.963
PP5
Variant 6-33789079-A-C is Pathogenic according to our data. Variant chr6-33789079-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 235192.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-33789079-A-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEMD2 | NM_181336.4 | c.38T>G | p.Leu13Arg | missense_variant | 1/9 | ENST00000293760.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEMD2 | ENST00000293760.10 | c.38T>G | p.Leu13Arg | missense_variant | 1/9 | 1 | NM_181336.4 | P1 | |
LEMD2 | ENST00000421671.6 | c.38T>G | p.Leu13Arg | missense_variant, NMD_transcript_variant | 1/9 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cataract 46 juvenile-onset Pathogenic:2
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Nov 01, 2015 | This variant co-segregates with juvenile cataracts in 39 family members (including 17 affected individuals [homozygous], 22 obligate carriers) across multiple sibships within a large Hutterite population. A potential association with sudden cardiac death is also observed. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 13, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;.
REVEL
Pathogenic
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0154);Gain of disorder (P = 0.0154);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at