6-33772927-AGAG-A

Position:

• chr6-33772927-AGAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181336.4(LEMD2):​c.1362-152_1362-150del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 659,974 control chromosomes in the GnomAD database, including 7,303 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1449 hom., cov: 30)
  • Exomes 𝑓: 0.14 (5854 hom.)
• Consequence: LEMD2 NM_181336.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.32

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-33772927-AGAG-A is Benign according to our data. Variant chr6-33772927-AGAG-A is described in ClinVar as [Benign]. Clinvar id is 1294878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LEMD2	NM_181336.4	c.1362-152_1362-150del		intron_variant		ENST00000293760.10
LEMD2	NM_001143944.1	c.456-152_456-150del		intron_variant
LEMD2	NM_001348709.2	c.456-152_456-150del		intron_variant
LEMD2	NM_001348710.2	c.963-152_963-150del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10	c.1362-152_1362-150del		intron_variant		1	NM_181336.4	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18311 AN: 152150 Hom.: 1448 Cov.: 30

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0466

Gnomad SAS AF: 0.0625

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.140 AC: 71325 AN: 507706 Hom.: 5854 AF XY: 0.138 AC XY: 36570 AN XY: 264838

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.0885

Gnomad4 SAS exome AF: 0.0715

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.120 AC: 18317 AN: 152268 Hom.: 1449 Cov.: 30 AF XY: 0.116 AC XY: 8616 AN XY: 74438

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0465

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.149

Alfa AF: 0.140 Hom.: 205

Bravo AF: 0.121

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs70996802; hg19: chr6-33740704;