Variant chr6-33772815-C-T 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.1362-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 1,590,830 control chromosomes in the GnomAD database, including 243,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.48 ( 19071 hom., cov: 33)

Exomes 𝑓: 0.55 ( 224154 hom. )

Consequence

LEMD2
NM_181336.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.39

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=-0.83).

BP6

Variant 6-33772815-C-T is Benign according to our data. Variant chr6-33772815-C-T is described in ClinVar as [Benign]. Clinvar id is 1279226.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
LEMD2	NM_181336.4 linkuse as main transcript	c.1362-37G>A	intron_variant	ENST00000293760.10
LEMD2	NM_001143944.1 linkuse as main transcript	c.456-37G>A	intron_variant
LEMD2	NM_001348709.2 linkuse as main transcript	c.456-37G>A	intron_variant
LEMD2	NM_001348710.2 linkuse as main transcript	c.963-37G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.1362-37G>A		intron_variant		1	NM_181336.4	P1	Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73459

AN:

151968

Hom.:

19066

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.665

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.506

GnomAD3 exomes

AF:

0.558

AC:

126538

AN:

226934

Hom.:

36398

AF XY:

0.567

AC XY:

69930

AN XY:

123322

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.821

Gnomad SAS exome

AF:

0.662

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.549

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.553

AC:

796198

AN:

1438744

Hom.:

224154

Cov.:

AF XY:

0.558

AC XY:

398457

AN XY:

713960

show subpopulations

Gnomad4 AFR exome

AF:

0.288

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.547

Gnomad4 EAS exome

AF:

0.819

Gnomad4 SAS exome

AF:

0.657

Gnomad4 FIN exome

AF:

0.534

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.547

GnomAD4 genome

AF:

0.483

AC:

73483

AN:

152086

Hom.:

19071

Cov.:

AF XY:

0.484

AC XY:

35963

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.546

Gnomad4 EAS

AF:

0.817

Gnomad4 SAS

AF:

0.665

Gnomad4 FIN

AF:

0.536

Gnomad4 NFE

AF:

0.546

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.506

Hom.:

3625

Bravo

AF:

0.472

Asia WGS

AF:

0.676

AC:

2353

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 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.74

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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