Genetic Variant EMP2:p.Ser156Ser (chr16-10532941-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_001424.6(EMP2):c.468C>T(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000593 in 1,601,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

EMP2
NM_001424.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.255

Publications

0 publications found

Variant links:

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

EMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 16-10532941-G-A is Benign according to our data. Variant chr16-10532941-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1581264.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.255 with no splicing effect.

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.468C>T	p.Ser156Ser	synonymous	Exon 5 of 5	NP_001415.1	P54851

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMP2	ENST00000359543.8	TSL:1 MANE Select	c.468C>T	p.Ser156Ser	synonymous	Exon 5 of 5	ENSP00000352540.3	P54851
EMP2	ENST00000536829.1	TSL:2	c.468C>T	p.Ser156Ser	synonymous	Exon 5 of 5	ENSP00000445712.1	P54851
EMP2	ENST00000867006.1		c.468C>T	p.Ser156Ser	synonymous	Exon 5 of 5	ENSP00000537065.1

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000775

AC:

AN:

245302

AF XY:

0.0000452

show subpopulations

Gnomad AFR exome

AF:

0.00100

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1449156

Hom.:

Cov.:

AF XY:

0.0000306

AC XY:

AN XY:

719966

show subpopulations

African (AFR)

AF:

0.000482

AC:

AN:

33166

American (AMR)

AF:

0.0000690

AC:

AN:

43462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25946

East Asian (EAS)

AF:

0.00

AC:

AN:

39254

South Asian (SAS)

AF:

0.0000239

AC:

AN:

83822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5300

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

1105268

Other (OTH)

AF:

0.0000668

AC:

AN:

59894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000362

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

41522

American (AMR)

AF:

0.000196

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000395

Hom.:

Bravo

AF:

0.000382

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

EMP2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.7

(source)

DANN

Benign

0.85

PhyloP100

-0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over