16-10532807-C-G

Variant names:

• chr16-10532807-C-G
• rs74007148
• NM_001424.6:c.*98G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001424.6(EMP2):​c.*98G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 203,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 22)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).

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.*98G>C		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.*98G>C		3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
	EMP2	ENST00000867006.1		c.*98G>C		3_prime_UTR	Exon 5 of 5	ENSP00000537065.1
	EMP2	ENST00000867008.1		c.*98G>C		3_prime_UTR	Exon 6 of 6	ENSP00000537067.1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 233 AN: 101930 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.00751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00159

Gnomad ASJ AF: 0.00427

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00781

Gnomad NFE AF: 0.0000725

Gnomad OTH AF: 0.00299

GnomAD4 exome AF: 0.00120 AC: 122 AN: 101988 Hom.: 0 Cov.: 3 AF XY: 0.00120 AC XY: 66 AN XY: 54860

African (AFR) AF: 0.0163 AC: 57 AN: 3498

American (AMR) AF: 0.000901 AC: 6 AN: 6658

Ashkenazi Jewish (ASJ) AF: 0.0180 AC: 32 AN: 1778

East Asian (EAS) AF: 0.00 AC: 0 AN: 5232

South Asian (SAS) AF: 0.00 AC: 0 AN: 8300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7038

Middle Eastern (MID) AF: 0.00937 AC: 3 AN: 320

European-Non Finnish (NFE) AF: 0.000262 AC: 17 AN: 64828

Other (OTH) AF: 0.00161 AC: 7 AN: 4336

GnomAD4 genome AF: 0.00228 AC: 232 AN: 101974 Hom.: 1 Cov.: 22 AF XY: 0.00238 AC XY: 109 AN XY: 45892

African (AFR) AF: 0.00750 AC: 201 AN: 26788

American (AMR) AF: 0.00158 AC: 10 AN: 6316

Ashkenazi Jewish (ASJ) AF: 0.00427 AC: 13 AN: 3044

East Asian (EAS) AF: 0.00 AC: 0 AN: 2980

South Asian (SAS) AF: 0.00 AC: 0 AN: 3082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.0000725 AC: 4 AN: 55200

Other (OTH) AF: 0.00297 AC: 4 AN: 1348

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism

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: rs74007148; hg19: chr16-10626664;