Variant 2-192057773-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016192.4(TMEFF2):c.442C>T(p.His148Tyr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00357 in 1,612,172 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 86 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 90 hom. )

Consequence

TMEFF2
NM_016192.4 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.87

Variant links:

Genes affected

TMEFF2 (HGNC:11867): (transmembrane protein with EGF like and two follistatin like domains 2) This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

TMEFF2 links:

CAVIN2-AS1 (HGNC:):

CAVIN2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020294785).

BP6

Variant 2-192057773-G-A is Benign according to our data. Variant chr2-192057773-G-A is described in ClinVar as [Benign]. Clinvar id is 775799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEFF2	NM_016192.4 linkuse as main transcript	c.442C>T	p.His148Tyr	missense_variant, splice_region_variant	5/10	ENST00000272771.10	NP_057276.2	Q9UIK5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEFF2	ENST00000272771.10 linkuse as main transcript	c.442C>T	p.His148Tyr	missense_variant, splice_region_variant	5/10	1	NM_016192.4	ENSP00000272771.5		Q9UIK5-1
TMEFF2	ENST00000392314.5 linkuse as main transcript	c.442C>T	p.His148Tyr	missense_variant, splice_region_variant	5/10	1		ENSP00000376128.1		Q9UIK5-2

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2789

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00884

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00503

AC:

1263

AN:

251064

Hom.:

AF XY:

0.00375

AC XY:

509

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.0655

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00203

AC:

2958

AN:

1459914

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1261

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.0644

Gnomad4 AMR exome

AF:

0.00459

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000243

Gnomad4 OTH exome

AF:

0.00499

GnomAD4 genome

AF:

0.0184

AC:

2802

AN:

152258

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1291

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0626

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00334

Hom.:

Bravo

AF:

0.0208

ESP6500AA

AF:

0.0640

AC:

282

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00624

AC:

758

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.075

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

T;D

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.057

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.30

MVP

0.65

MPC

0.75

ClinPred

0.011

GERP RS

4.0

Varity_R

0.096

gMVP

0.48

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over