16-10532807-C-T

Position:

• chr16-10532807-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001424.6(EMP2):​c.*98G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 203,584 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (28 hom., cov: 22)
  • Exomes 𝑓: 0.042 (45 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0280

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 16-10532807-C-T is Benign according to our data. Variant chr16-10532807-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1201301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*98G>A		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.*98G>A		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3
EMP2	ENST00000536829.1	c.*98G>A		downstream_gene_variant		2		ENSP00000445712.1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 2088 AN: 101872 Hom.: 28 Cov.: 22

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.00470

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.00714

Gnomad MID AF: 0.0703

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.0422 AC: 4292 AN: 101668 Hom.: 45 Cov.: 3 AF XY: 0.0412 AC XY: 2252 AN XY: 54700

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.00344

Gnomad4 SAS exome AF: 0.0203

Gnomad4 FIN exome AF: 0.00711

Gnomad4 NFE exome AF: 0.0506

Gnomad4 OTH exome AF: 0.0510

GnomAD4 genome AF: 0.0205 AC: 2090 AN: 101916 Hom.: 28 Cov.: 22 AF XY: 0.0206 AC XY: 946 AN XY: 45868

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0658

Gnomad4 EAS AF: 0.00470

Gnomad4 SAS AF: 0.0163

Gnomad4 FIN AF: 0.00714

Gnomad4 NFE AF: 0.0190

Gnomad4 OTH AF: 0.0252

Alfa AF: 0.00218 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 15, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	8.0
DANN	Benign	0.75

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: rs74007148; hg19: chr16-10626664;