Variant 6-33780115-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_181336.4(LEMD2):c.995A>G(p.Lys332Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,592,532 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

LEMD2
NM_181336.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.35

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]

LEMD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006903559).

BP6

Variant 6-33780115-T-C is Benign according to our data. Variant chr6-33780115-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2042860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LEMD2	NM_181336.4 linkuse as main transcript	c.995A>G	p.Lys332Arg	missense_variant	5/9	ENST00000293760.10
LEMD2	NM_001348710.2 linkuse as main transcript	c.596A>G	p.Lys199Arg	missense_variant	5/9
LEMD2	NM_001143944.1 linkuse as main transcript	c.89A>G	p.Lys30Arg	missense_variant	4/8
LEMD2	NM_001348709.2 linkuse as main transcript	c.89A>G	p.Lys30Arg	missense_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.995A>G	p.Lys332Arg	missense_variant	5/9	1	NM_181336.4	P1	Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.00203

AC:

309

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00692

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000572

AC:

125

AN:

218640

Hom.:

AF XY:

0.000451

AC XY:

AN XY:

117506

show subpopulations

Gnomad AFR exome

AF:

0.00645

Gnomad AMR exome

AF:

0.000885

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:

0.0000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000264

AC:

380

AN:

1440202

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

150

AN XY:

714188

show subpopulations

Gnomad4 AFR exome

AF:

0.00669

Gnomad4 AMR exome

AF:

0.000949

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000603

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000664

Gnomad4 OTH exome

AF:

0.000655

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152330

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00690

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000440

Hom.:

Bravo

AF:

0.00249

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000619

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

LEMD2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;.;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0069

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

M;M;.;.

MutationTaster

Benign

0.94

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.3

N;.;N;D

REVEL

Benign

0.082

Sift

Benign

0.093

T;.;T;D

Sift4G

Pathogenic

0.0

D;D;T;.

Polyphen

0.98

D;D;.;.

Vest4

0.41

MVP

0.73

MPC

0.51

ClinPred

0.044

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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