15-62819540-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015059.3(TLN2):ā€‹c.6796T>Gā€‹(p.Phe2266Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F2266L) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000025 ( 0 hom. )

Consequence

TLN2
NM_015059.3 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02
Variant links:
Genes affected
TLN2 (HGNC:15447): (talin 2) This gene encodes a protein related to talin 1, a cytoskeletal protein that plays a significant role in the assembly of actin filaments and in spreading and migration of various cell types, including fibroblasts and osteoclasts. This protein has a different pattern of expression compared to talin 1 but, like talin 1, is thought to associate with unique transmembrane receptors to form novel linkages between extracellular matrices and the actin cytoskeleton. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11391926).
BS2
High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TLN2NM_015059.3 linkc.6796T>G p.Phe2266Val missense_variant 53/59 ENST00000636159.2 NP_055874.2 Q9Y4G6
TLN2NM_001394547.1 linkc.6796T>G p.Phe2266Val missense_variant 52/58 NP_001381476.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TLN2ENST00000636159.2 linkc.6796T>G p.Phe2266Val missense_variant 53/595 NM_015059.3 ENSP00000490662.2 Q9Y4G6A0A1B0GVU7
TLN2ENST00000489129.5 linkn.4711T>G non_coding_transcript_exon_variant 21/271
TLN2ENST00000561311.5 linkc.6796T>G p.Phe2266Val missense_variant 52/585 ENSP00000453508.1 Q9Y4G6
TLN2ENST00000494733.5 linkc.3538T>G p.Phe1180Val missense_variant 26/325 ENSP00000453730.1 H0YMT1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152084
Hom.:
0
Cov.:
32
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:
0.000386
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:
0.00000398
AC:
1
AN:
251090
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135710
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461780
Hom.:
0
Cov.:
32
AF XY:
0.0000289
AC XY:
21
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000464
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152202
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000946
Bravo
AF:
0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.20
T;T;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.61
T;T;T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.90
L;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.65
N;.;N
Sift
Benign
0.29
T;.;T
Sift4G
Benign
0.30
T;.;T
Polyphen
0.0
B;.;.
Vest4
0.14
MutPred
0.32
Gain of MoRF binding (P = 0.1056);.;.;
MVP
0.10
MPC
0.29
ClinPred
0.18
T
GERP RS
4.6
Varity_R
0.089
gMVP
0.22

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.

Other links and lift over

dbSNP: rs3816988; hg19: chr15-63111739; API