16-10532740-ATTTTTTTT-ATTTTTT

Variant names:

• chr16-10532740-ATT-A
• rs35927182
• NM_001424.6:c.*163_*164delAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001424.6(EMP2):​c.*163_*164delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 203,112 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000042 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• Publications: 1 publications found

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]

EMP2 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	NM_001424.6	MANE Select	c.*163_*164delAA		3_prime_UTR	Exon 5 of 5	NP_001415.1	P54851

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	ENST00000359543.8	TSL:1 MANE Select	c.*163_*164delAA		3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
	EMP2	ENST00000867008.1		c.*163_*164delAA		splice_region	Exon 6 of 6	ENSP00000537067.1
	EMP2	ENST00000971799.1		c.*163_*164delAA		splice_region	Exon 6 of 6	ENSP00000641858.1

Frequencies

GnomAD3 genomes AF: 0.0000421 AC: 4 AN: 95104 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000370 AC: 4 AN: 108008 Hom.: 0 AF XY: 0.0000373 AC XY: 2 AN XY: 53664

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2222

American (AMR) AF: 0.00 AC: 0 AN: 1262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3400

East Asian (EAS) AF: 0.00 AC: 0 AN: 5280

South Asian (SAS) AF: 0.00 AC: 0 AN: 2504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 572

European-Non Finnish (NFE) AF: 0.0000473 AC: 4 AN: 84568

Other (OTH) AF: 0.00 AC: 0 AN: 5480

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000421 AC: 4 AN: 95104 Hom.: 0 Cov.: 0 AF XY: 0.0000457 AC XY: 2 AN XY: 43720

African (AFR) AF: 0.000145 AC: 4 AN: 27570

American (AMR) AF: 0.00 AC: 0 AN: 7098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2320

East Asian (EAS) AF: 0.00 AC: 0 AN: 3378

South Asian (SAS) AF: 0.00 AC: 0 AN: 3356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46388

Other (OTH) AF: 0.00 AC: 0 AN: 1258

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66

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

Other links and lift over

dbSNP: rs35927182; hg19: chr16-10626597;