Variant 6-33777105-C-G 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+33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,610,032 control chromosomes in the GnomAD database, including 131,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11383 hom., cov: 33)

Exomes 𝑓: 0.40 ( 119729 hom. )

Consequence

LEMD2
NM_181336.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.154

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=-0.85).

BP6

Variant 6-33777105-C-G is Benign according to our data. Variant chr6-33777105-C-G is described in ClinVar as [Benign]. Clinvar id is 1263137.Status of the report is criteria_provided_single_submitter, 1 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.1258+33G>C	intron_variant	ENST00000293760.10
LEMD2	NM_001143944.1 linkuse as main transcript	c.352+33G>C	intron_variant
LEMD2	NM_001348709.2 linkuse as main transcript	c.352+33G>C	intron_variant
LEMD2	NM_001348710.2 linkuse as main transcript	c.859+33G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.1258+33G>C		intron_variant		1	NM_181336.4	P1	Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57147

AN:

151994

Hom.:

11381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.442

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.771

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.364

GnomAD3 exomes

AF:

0.424

AC:

106648

AN:

251408

Hom.:

24720

AF XY:

0.434

AC XY:

58938

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.355

Gnomad EAS exome

AF:

0.784

Gnomad SAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.382

GnomAD4 exome

AF:

0.397

AC:

578538

AN:

1457920

Hom.:

119729

Cov.:

AF XY:

0.403

AC XY:

292316

AN XY:

725604

show subpopulations

Gnomad4 AFR exome

AF:

0.299

Gnomad4 AMR exome

AF:

0.353

Gnomad4 ASJ exome

AF:

0.360

Gnomad4 EAS exome

AF:

0.736

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.409

Gnomad4 NFE exome

AF:

0.375

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.376

AC:

57165

AN:

152112

Hom.:

11383

Cov.:

AF XY:

0.381

AC XY:

28312

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.349

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:

0.370

Alfa

AF:

0.363

Hom.:

1848

Bravo

AF:

0.367

Asia WGS

AF:

0.620

AC:

2157

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

-0.85

CADD

Benign

0.24

DANN

Benign

0.36

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