6-33772248-C-T

Position:

• chr6-33772248-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000293760.10(LEMD2):​c.*380G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 172,768 control chromosomes in the GnomAD database, including 11,124 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (9655 hom., cov: 33)
  • Exomes 𝑓: 0.36 (1469 hom.)
• Consequence: LEMD2 ENST00000293760.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEMD2	NM_181336.4	c.*380G>A		3_prime_UTR_variant	9/9	ENST00000293760.10	NP_851853.1
LEMD2	NM_001143944.1	c.*380G>A		3_prime_UTR_variant	8/8		NP_001137416.1
LEMD2	NM_001348709.2	c.*380G>A		3_prime_UTR_variant	9/9		NP_001335638.1
LEMD2	NM_001348710.2	c.*380G>A		3_prime_UTR_variant	9/9		NP_001335639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEMD2	ENST00000293760.10	c.*380G>A		3_prime_UTR_variant	9/9	1	NM_181336.4	ENSP00000293760	P1
LEMD2	ENST00000506578.5	c.*380G>A		3_prime_UTR_variant	3/3	5		ENSP00000423715
LEMD2	ENST00000511171.5	n.3844G>A		non_coding_transcript_exon_variant	5/5	2
LEMD2	ENST00000421671.6	c.*1153G>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	3		ENSP00000398733

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50833 AN: 151984 Hom.: 9652 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.356 AC: 7361 AN: 20666 Hom.: 1469 Cov.: 0 AF XY: 0.365 AC XY: 3889 AN XY: 10664

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.737

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.334 AC: 50842 AN: 152102 Hom.: 9655 Cov.: 33 AF XY: 0.339 AC XY: 25241 AN XY: 74358

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.331

Alfa AF: 0.350 Hom.: 6064

Bravo AF: 0.320

Asia WGS AF: 0.566 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.76

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: rs2296743; hg19: chr6-33740025;