Variant chr1-115050537-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005725.6(TSPAN2):c.619A>T(p.Ser207Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

TSPAN2
NM_005725.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09

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:

TSPAN2 (HGNC:):

TSPAN2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSPAN2	NM_005725.6 linkuse as main transcript	c.619A>T	p.Ser207Cys	missense_variant	8/8	ENST00000369516.7	NP_005716.2	O60636-1B2RD31
TSPAN2	NM_001308315.2 linkuse as main transcript	c.544A>T	p.Ser182Cys	missense_variant	7/7		NP_001295244.1	B1AKP1
TSPAN2	NM_001308316.2 linkuse as main transcript	c.535A>T	p.Ser179Cys	missense_variant	7/7		NP_001295245.1	O60636-2
TSPAN2	XM_016999996.2 linkuse as main transcript	c.460A>T	p.Ser154Cys	missense_variant	6/6		XP_016855485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSPAN2	ENST00000369516.7 linkuse as main transcript	c.619A>T	p.Ser207Cys	missense_variant	8/8	1	NM_005725.6	ENSP00000358529.2	O60636-1
TSPAN2	ENST00000433172.3 linkuse as main transcript	c.517A>T	p.Ser173Cys	missense_variant	7/7	1		ENSP00000415256.1	B1AKP2
TSPAN2	ENST00000369515.6 linkuse as main transcript	c.544A>T	p.Ser182Cys	missense_variant	7/7	3		ENSP00000358528.2	B1AKP1
TSPAN2	ENST00000491992.1 linkuse as main transcript	n.372A>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000801

AC:

AN:

249592

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000223

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000820

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000503

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

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

Dec 09, 2024

The c.619A>T (p.S207C) alteration is located in exon 8 (coding exon 8) of the TSPAN2 gene. This alteration results from a A to T substitution at nucleotide position 619, causing the serine (S) at amino acid position 207 to be replaced by a cysteine (C). 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

Uncertain

0.53

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Pathogenic

3.4

M;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.81

MVP

0.83

MPC

0.50

ClinPred

0.78

GERP RS

6.0

Varity_R

0.88

gMVP

0.89

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