Variant chr1-27880022-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105556.3(THEMIS2):c.614G>A(p.Arg205Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,607,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

THEMIS2
NM_001105556.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

THEMIS2 (HGNC:16839): (thymocyte selection associated family member 2) Predicted to be involved in T cell receptor signaling pathway and regulation of B cell activation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

THEMIS2 links:

THEMIS2 (HGNC:):

THEMIS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008401573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THEMIS2	NM_001105556.3 linkuse as main transcript	c.614G>A	p.Arg205Gln	missense_variant	3/6	ENST00000373921.8	NP_001099026.1	Q5TEJ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THEMIS2	ENST00000373921.8 linkuse as main transcript	c.614G>A	p.Arg205Gln	missense_variant	3/6	5	NM_001105556.3	ENSP00000363031.3		Q5TEJ8-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000442

AC:

110

AN:

248882

Hom.:

AF XY:

0.000431

AC XY:

AN XY:

134468

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000784

Gnomad ASJ exome

AF:

0.00334

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000661

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000330

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.000265

AC:

385

AN:

1455344

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

209

AN XY:

722650

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000808

Gnomad4 ASJ exome

AF:

0.00432

Gnomad4 EAS exome

AF:

0.000481

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.000583

GnomAD4 genome

AF:

0.000243

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000329

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000534

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

Jul 20, 2022

The c.614G>A (p.R205Q) alteration is located in exon 3 (coding exon 3) of the THEMIS2 gene. This alteration results from a G to A substitution at nucleotide position 614, causing the arginine (R) at amino acid position 205 to be replaced by a glutamine (Q). 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

0.086

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.5

DANN

Benign

0.94

DEOGEN2

Benign

0.016

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.0084

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.62

N;N;N

REVEL

Benign

0.059

Sift

Benign

0.096

T;T;D

Sift4G

Benign

0.32

T;T;T

Polyphen

0.11

B;P;D

Vest4

0.13

MVP

0.030

MPC

0.50

ClinPred

0.027

GERP RS

-9.6

Varity_R

0.029

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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