rs2395402

Variant names:

• chr6-33785896-G-A
• rs2395402
• NM_181336.4:c.777+838C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-33785896-G-A
• chr6-33785896-G-C
• chr6-33785896-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181336.4(LEMD2):​c.777+838C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,148 control chromosomes in the GnomAD database, including 18,970 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 0.48 (18970 hom., cov: 33)
• Consequence: LEMD2 NM_181336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• Marbach-Rustad progeroid syndrome

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• cataract 46 juvenile-onset

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• early-onset posterior subcapsular cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEMD2	NM_181336.4	c.777+838C>T		intron_variant	Intron 2 of 8	ENST00000293760.10	NP_851853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEMD2	ENST00000293760.10	c.777+838C>T		intron_variant	Intron 2 of 8	1	NM_181336.4	ENSP00000293760.5

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73105 AN: 152030 Hom.: 18965 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.481 AC: 73129 AN: 152148 Hom.: 18970 Cov.: 33 AF XY: 0.482 AC XY: 35819 AN XY: 74390

African (AFR) AF: 0.286 AC: 11859 AN: 41500

American (AMR) AF: 0.480 AC: 7333 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1893 AN: 3468

East Asian (EAS) AF: 0.817 AC: 4236 AN: 5184

South Asian (SAS) AF: 0.665 AC: 3208 AN: 4826

European-Finnish (FIN) AF: 0.538 AC: 5688 AN: 10580

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37135 AN: 67996

Other (OTH) AF: 0.510 AC: 1078 AN: 2112

Alfa AF: 0.525 Hom.: 71008

Bravo AF: 0.469

Asia WGS AF: 0.677 AC: 2355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.50
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2395402; hg19: chr6-33753673;