Variant 1-115062151-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005725.6(TSPAN2):c.254A>C(p.Gln85Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000188 in 1,595,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TSPAN2
NM_005725.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN2	NM_005725.6 linkuse as main transcript	c.254A>C	p.Gln85Pro	missense_variant	3/8	ENST00000369516.7	NP_005716.2	O60636-1B2RD31
TSPAN2	NM_001308315.2 linkuse as main transcript	c.254A>C	p.Gln85Pro	missense_variant	3/7		NP_001295244.1	B1AKP1
TSPAN2	NM_001308316.2 linkuse as main transcript	c.254A>C	p.Gln85Pro	missense_variant	3/7		NP_001295245.1	O60636-2
TSPAN2	XM_016999996.2 linkuse as main transcript	c.254A>C	p.Gln85Pro	missense_variant	3/6		XP_016855485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSPAN2	ENST00000369516.7 linkuse as main transcript	c.254A>C	p.Gln85Pro	missense_variant	3/8	1	NM_005725.6	ENSP00000358529.2	O60636-1
TSPAN2	ENST00000433172.3 linkuse as main transcript	c.236A>C	p.Gln79Pro	missense_variant	3/7	1		ENSP00000415256.1	B1AKP2
TSPAN2	ENST00000369515.6 linkuse as main transcript	c.254A>C	p.Gln85Pro	missense_variant	3/7	3		ENSP00000358528.2	B1AKP1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000906

AC:

AN:

220686

Hom.:

AF XY:

0.00000845

AC XY:

AN XY:

118394

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000727

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1443252

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000826

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

The c.254A>C (p.Q85P) alteration is located in exon 3 (coding exon 3) of the TSPAN2 gene. This alteration results from a A to C substitution at nucleotide position 254, causing the glutamine (Q) at amino acid position 85 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.91

D;T;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Pathogenic

0.66

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.32

MutPred

0.84

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;

MVP

0.76

MPC

0.54

ClinPred

0.75

GERP RS

5.6

Varity_R

0.75

gMVP

0.92

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