Variant chr6-33772605-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.*23C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,604,308 control chromosomes in the GnomAD database, including 235,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 17677 hom., cov: 34)

Exomes 𝑓: 0.54 ( 218134 hom. )

Consequence

LEMD2
NM_181336.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.749

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=-0.77).

BP6

Variant 6-33772605-G-A is Benign according to our data. Variant chr6-33772605-G-A is described in ClinVar as [Benign]. Clinvar id is 1289212.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
LEMD2	NM_181336.4 linkuse as main transcript	c.*23C>T	3_prime_UTR_variant	9/9	ENST00000293760.10
LEMD2	NM_001143944.1 linkuse as main transcript	c.*23C>T	3_prime_UTR_variant	8/8
LEMD2	NM_001348709.2 linkuse as main transcript	c.*23C>T	3_prime_UTR_variant	9/9
LEMD2	NM_001348710.2 linkuse as main transcript	c.*23C>T	3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.*23C>T		3_prime_UTR_variant	9/9	1	NM_181336.4	P1	Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69408

AN:

152044

Hom.:

17669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.781

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.481

GnomAD3 exomes

AF:

0.535

AC:

130642

AN:

244046

Hom.:

36532

AF XY:

0.546

AC XY:

71946

AN XY:

131854

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.546

Gnomad EAS exome

AF:

0.782

Gnomad SAS exome

AF:

0.602

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.543

AC:

788243

AN:

1452146

Hom.:

218134

Cov.:

AF XY:

0.546

AC XY:

394269

AN XY:

721596

show subpopulations

Gnomad4 AFR exome

AF:

0.217

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.599

Gnomad4 FIN exome

AF:

0.533

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.531

GnomAD4 genome

AF:

0.456

AC:

69421

AN:

152162

Hom.:

17677

Cov.:

AF XY:

0.457

AC XY:

33977

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.542

Gnomad4 EAS

AF:

0.781

Gnomad4 SAS

AF:

0.607

Gnomad4 FIN

AF:

0.536

Gnomad4 NFE

AF:

0.542

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.489

Hom.:

3858

Bravo

AF:

0.442

Asia WGS

AF:

0.622

AC:

2167

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

-0.77

CADD

Benign

DANN

Benign

0.73

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