16-10532773-T-C

Position:

• chr16-10532773-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001424.6(EMP2):​c.*132A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 372,924 control chromosomes in the GnomAD database, including 722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (73 hom., cov: 29)
  • Exomes 𝑓: 0.020 (649 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-10532773-T-C is Benign according to our data. Variant chr16-10532773-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1191904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0203 (4646/228708) while in subpopulation MID AF= 0.0262 (22/840). AF 95% confidence interval is 0.02. There are 649 homozygotes in gnomad4_exome. There are 2306 alleles in male gnomad4_exome subpopulation. Median coverage is 5. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 73 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*132A>G		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.*132A>G		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.00882 AC: 1271 AN: 144134 Hom.: 73 Cov.: 29

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00337

Gnomad ASJ AF: 0.00323

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.00466

Gnomad FIN AF: 0.00408

Gnomad MID AF: 0.0329

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00837

GnomAD4 exome AF: 0.0203 AC: 4646 AN: 228708 Hom.: 649 Cov.: 5 AF XY: 0.0205 AC XY: 2306 AN XY: 112744

Gnomad4 AFR exome AF: 0.0166

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0173

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.0228

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0216

GnomAD4 genome AF: 0.00882 AC: 1272 AN: 144216 Hom.: 73 Cov.: 29 AF XY: 0.00806 AC XY: 565 AN XY: 70058

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.00337

Gnomad4 ASJ AF: 0.00323

Gnomad4 EAS AF: 0.00120

Gnomad4 SAS AF: 0.00467

Gnomad4 FIN AF: 0.00408

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00778

Alfa AF: 0.0105 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.78

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: rs945279078; hg19: chr16-10626630;