1-115058953-T-G

Position:

• chr1-115058953-T-G

Variant summary

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

The NM_005725.6(TSPAN2):​c.374A>C​(p.Glu125Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TSPAN2 NM_005725.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.14

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]

ACMG classification

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	c.374A>C	p.Glu125Ala	missense_variant	5/8	ENST00000369516.7	NP_005716.2
TSPAN2	NM_001308315.2	c.299A>C	p.Glu100Ala	missense_variant	4/7		NP_001295244.1
TSPAN2	NM_001308316.2	c.374A>C	p.Glu125Ala	missense_variant	5/7		NP_001295245.1
TSPAN2	XM_016999996.2	c.299A>C	p.Glu100Ala	missense_variant	4/6		XP_016855485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSPAN2	ENST00000369516.7	c.374A>C	p.Glu125Ala	missense_variant	5/8	1	NM_005725.6	ENSP00000358529.2
TSPAN2	ENST00000433172.3	c.356A>C	p.Glu119Ala	missense_variant	5/7	1		ENSP00000415256.1
TSPAN2	ENST00000369515.6	c.299A>C	p.Glu100Ala	missense_variant	4/7	3		ENSP00000358528.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.374A>C (p.E125A) alteration is located in exon 5 (coding exon 5) of the TSPAN2 gene. This alteration results from a A to C substitution at nucleotide position 374, causing the glutamic acid (E) at amino acid position 125 to be replaced by an alanine (A). 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	0.18
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;.
Eigen	Benign	0.059
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.079	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.54
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.31	T;T;T
Polyphen		0.035	B;.;.
Vest4		0.44
MutPred		0.49		Loss of phosphorylation at Y128 (P = 0.1157);.;.;
MVP		0.67
MPC		0.19
ClinPred		0.74	D
GERP RS		5.8
Varity_R		0.32
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-115601574;