1-115072974-A-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005725.6(TSPAN2):āc.103T>Cā(p.Trp35Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,614,030 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000012 ( 0 hom. )
Consequence
TSPAN2
NM_005725.6 missense
NM_005725.6 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 5.75
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.988
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TSPAN2 | NM_005725.6 | c.103T>C | p.Trp35Arg | missense_variant | 2/8 | ENST00000369516.7 | NP_005716.2 | |
TSPAN2 | NM_001308315.2 | c.103T>C | p.Trp35Arg | missense_variant | 2/7 | NP_001295244.1 | ||
TSPAN2 | NM_001308316.2 | c.103T>C | p.Trp35Arg | missense_variant | 2/7 | NP_001295245.1 | ||
TSPAN2 | XM_016999996.2 | c.103T>C | p.Trp35Arg | missense_variant | 2/6 | XP_016855485.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSPAN2 | ENST00000369516.7 | c.103T>C | p.Trp35Arg | missense_variant | 2/8 | 1 | NM_005725.6 | ENSP00000358529.2 | ||
TSPAN2 | ENST00000433172.3 | c.85T>C | p.Trp29Arg | missense_variant | 2/7 | 1 | ENSP00000415256.1 | |||
TSPAN2 | ENST00000369515.6 | c.103T>C | p.Trp35Arg | missense_variant | 2/7 | 3 | ENSP00000358528.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727238
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74320
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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 | Nov 18, 2022 | The c.103T>C (p.W35R) alteration is located in exon 2 (coding exon 2) of the TSPAN2 gene. This alteration results from a T to C substitution at nucleotide position 103, causing the tryptophan (W) at amino acid position 35 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of methylation at W35 (P = 0.0036);Gain of methylation at W35 (P = 0.0036);.;
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at