6-33772548-G-C

Position:

• chr6-33772548-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181336.4(LEMD2):​c.*80C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,372,666 control chromosomes in the GnomAD database, including 38,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3784 hom., cov: 34)
  • Exomes 𝑓: 0.24 (34597 hom.)
• Consequence: LEMD2 NM_181336.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.686

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-33772548-G-C is Benign according to our data. Variant chr6-33772548-G-C is described in ClinVar as [Benign]. Clinvar id is 1242353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEMD2	NM_181336.4	c.*80C>G		3_prime_UTR_variant	9/9	ENST00000293760.10	NP_851853.1
LEMD2	NM_001348710.2	c.*80C>G		3_prime_UTR_variant	9/9		NP_001335639.1
LEMD2	NM_001143944.1	c.*80C>G		3_prime_UTR_variant	8/8		NP_001137416.1
LEMD2	NM_001348709.2	c.*80C>G		3_prime_UTR_variant	9/9		NP_001335638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEMD2	ENST00000293760	c.*80C>G		3_prime_UTR_variant	9/9	1	NM_181336.4	ENSP00000293760.5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32789 AN: 152116 Hom.: 3780 Cov.: 34

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.235 AC: 286931 AN: 1220432 Hom.: 34597 Cov.: 16 AF XY: 0.234 AC XY: 142296 AN XY: 607958

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.215 AC: 32793 AN: 152234 Hom.: 3784 Cov.: 34 AF XY: 0.223 AC XY: 16627 AN XY: 74428

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.179

Alfa AF: 0.140 Hom.: 246

Bravo AF: 0.210

Asia WGS AF: 0.174 AC: 605 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 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.72

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: rs11755593; hg19: chr6-33740325; COSMIC: COSV53393421; COSMIC: COSV53393421;