rs2354420

chr16-10569181-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EMP2	NM_001424.6	c.-61+11368A>G		intron_variant		ENST00000359543.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMP2	ENST00000359543.8	c.-61+11368A>G		intron_variant		1	NM_001424.6	P1
EMP2	ENST00000342147.4	n.84+11368A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.0939

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.160

Alfa AF: 0.188 Hom.: 1321

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

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: rs2354420; hg19: chr16-10663038;