Variant 1-115058974-C-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_005725.6(TSPAN2):c.353G>T(p.Arg118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,611,862 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.015 ( 57 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 54 hom. )

Consequence

TSPAN2
NM_005725.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.30

Variant links:

Genes affected

TSPAN2 (HGNC:20659): (tetraspanin 2) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

TSPAN2 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=0.004477352).

BP6

Variant 1-115058974-C-A is Benign according to our data. Variant chr1-115058974-C-A is described in ClinVar as [Benign]. Clinvar id is 791110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN2	NM_005725.6 linkuse as main transcript	c.353G>T	p.Arg118Leu	missense_variant	5/8	ENST00000369516.7	NP_005716.2	O60636-1B2RD31
TSPAN2	NM_001308315.2 linkuse as main transcript	c.278G>T	p.Arg93Leu	missense_variant	4/7		NP_001295244.1	B1AKP1
TSPAN2	NM_001308316.2 linkuse as main transcript	c.353G>T	p.Arg118Leu	missense_variant	5/7		NP_001295245.1	O60636-2
TSPAN2	XM_016999996.2 linkuse as main transcript	c.278G>T	p.Arg93Leu	missense_variant	4/6		XP_016855485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSPAN2	ENST00000369516.7 linkuse as main transcript	c.353G>T	p.Arg118Leu	missense_variant	5/8	1	NM_005725.6	ENSP00000358529.2	O60636-1
TSPAN2	ENST00000433172.3 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	5/7	1		ENSP00000415256.1	B1AKP2
TSPAN2	ENST00000369515.6 linkuse as main transcript	c.278G>T	p.Arg93Leu	missense_variant	4/7	3		ENSP00000358528.2	B1AKP1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2232

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00379

AC:

947

AN:

249808

Hom.:

AF XY:

0.00259

AC XY:

350

AN XY:

134944

show subpopulations

Gnomad AFR exome

AF:

0.0505

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00161

AC:

2347

AN:

1459716

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1018

AN XY:

726092

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

AF:

0.0147

AC:

2240

AN:

152146

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1038

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0506

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.000903

Hom.:

Bravo

AF:

0.0168

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0538

AC:

237

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00464

AC:

564

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;.

Eigen

Benign

0.19

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.033

D;T;D

Sift4G

Benign

0.077

T;T;T

Polyphen

0.75

P;.;.

Vest4

0.45

MVP

0.77

MPC

0.29

ClinPred

0.041

GERP RS

4.9

Varity_R

0.30

gMVP

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

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