16-10569181-T-C

Variant names:

• chr16-10569181-T-C
• rs2354420
• NM_001424.6:c.-61+11368A>G

Variant summary

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

The NM_001424.6(EMP2):​c.-61+11368A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,210 control chromosomes in the GnomAD database, including 2,409 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 0.16 (2409 hom., cov: 31)
• Consequence: EMP2 NM_001424.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 7 publications found

Genes affected

EMP2 (HGNC:3334): (epithelial membrane protein 2) This gene encodes a tetraspan protein of the PMP22/EMP family. The encoded protein regulates cell membrane composition. It has been associated with various functions including endocytosis, cell signaling, cell proliferation, cell migration, cell adhesion, cell death, cholesterol homeostasis, urinary albumin excretion, and embryo implantation. It is known to negatively regulate caveolin-1, a scaffolding protein which is the main component of the caveolae plasma membrane invaginations found in most cell types. Through activation of PTK2 it positively regulates vascular endothelial growth factor A. It also modulates the function of specific integrin isomers in the plasma membrane. Up-regulation of this gene has been linked to cancer progression in multiple different tissues. Mutations in this gene have been associated with nephrotic syndrome type 10 (NPHS10). [provided by RefSeq, Mar 2015]

EMP2 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMP2	NM_001424.6	c.-61+11368A>G		intron_variant	Intron 1 of 4	ENST00000359543.8	NP_001415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543.8	c.-61+11368A>G		intron_variant	Intron 1 of 4	1	NM_001424.6	ENSP00000352540.3
EMP2	ENST00000342147.4	n.84+11368A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23914 AN: 152090 Hom.: 2411 Cov.: 31

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.157 AC: 23898 AN: 152210 Hom.: 2409 Cov.: 31 AF XY: 0.157 AC XY: 11712 AN XY: 74410

African (AFR) AF: 0.0430 AC: 1787 AN: 41552

American (AMR) AF: 0.158 AC: 2414 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3468

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5176

South Asian (SAS) AF: 0.0939 AC: 453 AN: 4826

European-Finnish (FIN) AF: 0.259 AC: 2737 AN: 10578

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14994 AN: 68002

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.174 Hom.: 2298

Bravo AF: 0.146

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.82
DANN	Benign	0.49
PhyloP100		-1.8
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: rs2354420; hg19: chr16-10663038;