16-10532752-T-TTTTTTC

Position:

• chr16-10532752-T-TTTTTTC

Variant summary

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

The NM_001424.6(EMP2):​c.*147_*152dupGAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 220,662 control chromosomes in the GnomAD database, including 6,711 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2442 hom., cov: 27)
  • Exomes 𝑓: 0.075 (4269 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.44

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 16-10532752-T-TTTTTTC is Benign according to our data. Variant chr16-10532752-T-TTTTTTC is described in ClinVar as [Benign]. Clinvar id is 1229140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*147_*152dupGAAAAA		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.*147_*152dupGAAAAA		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 14133 AN: 73458 Hom.: 2447 Cov.: 27

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.0750 AC: 11043 AN: 147188 Hom.: 4269 Cov.: 5 AF XY: 0.0752 AC XY: 5476 AN XY: 72852

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.0395

Gnomad4 SAS exome AF: 0.0417

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.0859

Gnomad4 OTH exome AF: 0.0498

GnomAD4 genome AF: 0.192 AC: 14120 AN: 73474 Hom.: 2442 Cov.: 27 AF XY: 0.183 AC XY: 6251 AN XY: 34216

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.169

Alfa AF: 0.0237 Hom.: 67

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

Mar 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555458377; hg19: chr16-10626609;