Variant 6-33777037-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_181336.4(LEMD2):c.1278C>T(p.Tyr426Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,614,106 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 16 hom. )

Consequence

LEMD2
NM_181336.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.202

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:

LEMD2 (HGNC:):

LEMD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 6-33777037-G-A is Benign according to our data. Variant chr6-33777037-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1545075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.202 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LEMD2	NM_181336.4 linkuse as main transcript	c.1278C>T	p.Tyr426Tyr	synonymous_variant	8/9	ENST00000293760.10	NP_851853.1
LEMD2	NM_001348710.2 linkuse as main transcript	c.879C>T	p.Tyr293Tyr	synonymous_variant	8/9		NP_001335639.1
LEMD2	NM_001143944.1 linkuse as main transcript	c.372C>T	p.Tyr124Tyr	synonymous_variant	7/8		NP_001137416.1
LEMD2	NM_001348709.2 linkuse as main transcript	c.372C>T	p.Tyr124Tyr	synonymous_variant	8/9		NP_001335638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEMD2	ENST00000293760.10 linkuse as main transcript	c.1278C>T	p.Tyr426Tyr	synonymous_variant	8/9	1	NM_181336.4	ENSP00000293760.5		Q8NC56-1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00563

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00406

AC:

1022

AN:

251476

Hom.:

AF XY:

0.00429

AC XY:

583

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00577

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00469

AC:

6854

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

3425

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00438

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00340

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00537

Gnomad4 OTH exome

AF:

0.00363

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152324

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00563

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00492

Hom.:

Bravo

AF:

0.00380

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	LEMD2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 08, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.7

DANN

Benign

0.57

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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