6-33777294-C-T

Position:

• chr6-33777294-C-T

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.1157-55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,190,158 control chromosomes in the GnomAD database, including 99,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10715 hom., cov: 33)
  • Exomes 𝑓: 0.40 (88937 hom.)
• Consequence: LEMD2 NM_181336.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.746

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 6-33777294-C-T is Benign according to our data. Variant chr6-33777294-C-T is described in ClinVar as [Benign]. Clinvar id is 1181735.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	HGVSp	Effect	#exon/exons	MANE	UniProt
LEMD2	NM_181336.4	c.1157-55G>A		intron_variant		ENST00000293760.10
LEMD2	NM_001143944.1	c.251-55G>A		intron_variant
LEMD2	NM_001348709.2	c.251-55G>A		intron_variant
LEMD2	NM_001348710.2	c.758-55G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEMD2	ENST00000293760.10	c.1157-55G>A		intron_variant		1	NM_181336.4	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54685 AN: 152030 Hom.: 10715 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.404 AC: 419218 AN: 1038010 Hom.: 88937 AF XY: 0.411 AC XY: 220333 AN XY: 536310

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.736

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.360 AC: 54703 AN: 152148 Hom.: 10715 Cov.: 33 AF XY: 0.365 AC XY: 27136 AN XY: 74370

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.359

Alfa AF: 0.382 Hom.: 26268

Bravo AF: 0.347

Asia WGS AF: 0.617 AC: 2148 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	-0.78
CADD	Benign	15
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2296748; hg19: chr6-33745071; COSMIC: COSV53395673; COSMIC: COSV53395673;