16-10532763-T-TC

Position:

• chr16-10532763-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001424.6(EMP2):​c.*141_*142insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (416 hom., cov: 0)
  • Exomes 𝑓: 0.0044 (152 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.504

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 -10 ACMG points.

• BP6: Variant 16-10532763-T-TC is Benign according to our data. Variant chr16-10532763-T-TC is described in ClinVar as [Benign]. Clinvar id is 1237080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*141_*142insG		3_prime_UTR_variant	5/5	ENST00000359543.8	NP_001415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543	c.*141_*142insG		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 6644 AN: 97136 Hom.: 417 Cov.: 0

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.0700

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0272

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.00439 AC: 506 AN: 115326 Hom.: 152 Cov.: 0 AF XY: 0.00430 AC XY: 248 AN XY: 57700

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.000438

Gnomad4 ASJ exome AF: 0.00155

Gnomad4 EAS exome AF: 0.00202

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.000175

Gnomad4 NFE exome AF: 0.00460

Gnomad4 OTH exome AF: 0.00461

GnomAD4 genome AF: 0.0683 AC: 6641 AN: 97186 Hom.: 416 Cov.: 0 AF XY: 0.0615 AC XY: 2848 AN XY: 46304

Gnomad4 AFR AF: 0.0840

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.0485

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.0603

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

Dec 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs35468276; hg19: chr16-10626620;