16-10532740-ATTTTTTTT-ATTTTTTTTTT

Variant names:

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

Variant summary

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

The NM_001424.6(EMP2):​c.*163_*164dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• Publications: 0 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_*164dupAA		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_*164dupAA		3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
	EMP2	ENST00000867008.1		c.*163_*164dupAA		splice_region	Exon 6 of 6	ENSP00000537067.1
	EMP2	ENST00000971799.1		c.*163_*164dupAA		splice_region	Exon 6 of 6	ENSP00000641858.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000926 AC: 1 AN: 108018 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 53668

⚠️ 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: 2722

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

European-Non Finnish (NFE) AF: 0.0000118 AC: 1 AN: 84574

Other (OTH) AF: 0.00 AC: 0 AN: 5482

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35927182; hg19: chr16-10626597;