rs2296743

Positions:

• chr6-33772248-C-A
• chr6-33772248-C-G
• chr6-33772248-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181336.4(LEMD2):​c.*380G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LEMD2 NM_181336.4 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEMD2	NM_181336.4	c.*380G>T		3_prime_UTR_variant	9/9	ENST00000293760.10	NP_851853.1
LEMD2	NM_001143944.1	c.*380G>T		3_prime_UTR_variant	8/8		NP_001137416.1
LEMD2	NM_001348709.2	c.*380G>T		3_prime_UTR_variant	9/9		NP_001335638.1
LEMD2	NM_001348710.2	c.*380G>T		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>T		3_prime_UTR_variant	9/9	1	NM_181336.4	ENSP00000293760	P1
LEMD2	ENST00000506578.5	c.*380G>T		3_prime_UTR_variant	3/3	5		ENSP00000423715
LEMD2	ENST00000511171.5	n.3844G>T		non_coding_transcript_exon_variant	5/5	2
LEMD2	ENST00000421671.6	c.*1153G>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	3		ENSP00000398733

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 20772 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10718

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.76
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2

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;