Variant 6-33777134-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_181336.4(LEMD2):c.1258+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000519 in 1,612,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 0 hom. )

Consequence

LEMD2
NM_181336.4 splice_region, intron

Scores

Splicing: ADA: 0.008947

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.664

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:

LEMD2 (HGNC:):

LEMD2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 6-33777134-G-A is Benign according to our data. Variant chr6-33777134-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2069437.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-33777134-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
LEMD2	NM_181336.4 linkuse as main transcript	c.1258+4C>T	splice_region_variant, intron_variant	ENST00000293760.10	NP_851853.1
LEMD2	NM_001348710.2 linkuse as main transcript	c.859+4C>T	splice_region_variant, intron_variant		NP_001335639.1
LEMD2	NM_001143944.1 linkuse as main transcript	c.352+4C>T	splice_region_variant, intron_variant		NP_001137416.1
LEMD2	NM_001348709.2 linkuse as main transcript	c.352+4C>T	splice_region_variant, intron_variant		NP_001335638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.1258+4C>T		splice_region_variant, intron_variant		1	NM_181336.4	ENSP00000293760.5		Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000597

AC:

150

AN:

251452

Hom.:

AF XY:

0.000655

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000527

AC:

770

AN:

1460696

Hom.:

Cov.:

AF XY:

0.000534

AC XY:

388

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00141

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.000478

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.000440

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000488

Hom.:

Bravo

AF:

0.000264

EpiCase

AF:

0.00180

EpiControl

AF:

0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LEMD2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0089

dbscSNV1_RF

Benign

0.048

SpliceAI score (max)

0.090

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