Variant chr6-33776934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181336.4(LEMD2):c.1361+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,600,278 control chromosomes in the GnomAD database, including 129,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10708 hom., cov: 32)

Exomes 𝑓: 0.40 ( 118355 hom. )

Consequence

LEMD2
NM_181336.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0550

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-33776934-C-T is Benign according to our data. Variant chr6-33776934-C-T is described in ClinVar as [Benign]. Clinvar id is 1252205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
LEMD2	NM_181336.4 linkuse as main transcript	c.1361+20G>A	intron_variant	ENST00000293760.10
LEMD2	NM_001143944.1 linkuse as main transcript	c.455+20G>A	intron_variant
LEMD2	NM_001348709.2 linkuse as main transcript	c.455+20G>A	intron_variant
LEMD2	NM_001348710.2 linkuse as main transcript	c.962+20G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.1361+20G>A		intron_variant		1	NM_181336.4	P1	Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54643

AN:

151876

Hom.:

10708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.420

AC:

104458

AN:

248568

Hom.:

24007

AF XY:

0.431

AC XY:

57959

AN XY:

134460

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.355

Gnomad EAS exome

AF:

0.783

Gnomad SAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.396

AC:

572802

AN:

1448284

Hom.:

118355

Cov.:

AF XY:

0.402

AC XY:

289765

AN XY:

721106

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.346

Gnomad4 ASJ exome

AF:

0.360

Gnomad4 EAS exome

AF:

0.737

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.395

GnomAD4 genome

AF:

0.360

AC:

54661

AN:

151994

Hom.:

10708

Cov.:

AF XY:

0.365

AC XY:

27114

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.771

Gnomad4 SAS

AF:

0.602

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.356

Hom.:

1797

Bravo

AF:

0.347

Asia WGS

AF:

0.617

AC:

2148

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.5

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

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