Variant 6-33777103-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_181336.4(LEMD2):c.1258+35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0074 in 1,610,162 control chromosomes in the GnomAD database, including 703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 335 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 368 hom. )

Consequence

LEMD2
NM_181336.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-33777103-G-A is Benign according to our data. Variant chr6-33777103-G-A is described in ClinVar as [Benign]. Clinvar id is 1237683.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
LEMD2	NM_181336.4 linkuse as main transcript	c.1258+35C>T	intron_variant	ENST00000293760.10
LEMD2	NM_001143944.1 linkuse as main transcript	c.352+35C>T	intron_variant
LEMD2	NM_001348709.2 linkuse as main transcript	c.352+35C>T	intron_variant
LEMD2	NM_001348710.2 linkuse as main transcript	c.859+35C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.1258+35C>T		intron_variant		1	NM_181336.4	P1	Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.0360

AC:

5472

AN:

152184

Hom.:

335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.0267

GnomAD3 exomes

AF:

0.0106

AC:

2673

AN:

251424

Hom.:

137

AF XY:

0.00793

AC XY:

1077

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000721

Gnomad OTH exome

AF:

0.00570

GnomAD4 exome

AF:

0.00441

AC:

6430

AN:

1457860

Hom.:

368

Cov.:

AF XY:

0.00382

AC XY:

2774

AN XY:

725608

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.00769

Gnomad4 ASJ exome

AF:

0.0123

Gnomad4 EAS exome

AF:

0.00222

Gnomad4 SAS exome

AF:

0.000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000365

Gnomad4 OTH exome

AF:

0.00899

GnomAD4 genome

AF:

0.0360

AC:

5482

AN:

152302

Hom.:

335

Cov.:

AF XY:

0.0348

AC XY:

2590

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000661

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0418

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.038

DANN

Benign

0.46

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