Variant rs3816988 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015059.3(TLN2):c.6796T>C(p.Phe2266Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,722 control chromosomes in the GnomAD database, including 24,417 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.18 ( 2416 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22001 hom. )

Consequence

TLN2
NM_015059.3 missense

Scores

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]

TLN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.6405873E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLN2	NM_015059.3 linkuse as main transcript	c.6796T>C	p.Phe2266Leu	missense_variant	53/59	ENST00000636159.2
TLN2	NM_001394547.1 linkuse as main transcript	c.6796T>C	p.Phe2266Leu	missense_variant	52/58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TLN2	ENST00000636159.2 linkuse as main transcript	c.6796T>C	p.Phe2266Leu	missense_variant	53/59	5	NM_015059.3	P1
TLN2	ENST00000489129.5 linkuse as main transcript	n.4711T>C		non_coding_transcript_exon_variant	21/27	1
TLN2	ENST00000561311.5 linkuse as main transcript	c.6796T>C	p.Phe2266Leu	missense_variant	52/58	5		P1
TLN2	ENST00000494733.5 linkuse as main transcript	c.3538T>C	p.Phe1180Leu	missense_variant	26/32	5

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26622

AN:

152046

Hom.:

2408

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.0764

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.162

AC:

40783

AN:

251090

Hom.:

3607

AF XY:

0.165

AC XY:

22380

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.0738

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.171

AC:

249884

AN:

1461558

Hom.:

22001

Cov.:

AF XY:

0.172

AC XY:

124736

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.0780

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.175

AC:

26663

AN:

152164

Hom.:

2416

Cov.:

AF XY:

0.175

AC XY:

13017

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.0764

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.166

Hom.:

5469

Bravo

AF:

0.176

TwinsUK

AF:

0.186

AC:

689

ALSPAC

AF:

0.181

AC:

699

ESP6500AA

AF:

0.193

AC:

851

ESP6500EA

AF:

0.171

AC:

1472

ExAC

AF:

0.164

AC:

19893

EpiCase

AF:

0.164

EpiControl

AF:

0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.31

T;T;T

MetaRNN

Benign

0.00086

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;.;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.55

PROVEAN

Benign

1.4

N;.;N

Sift

Benign

0.40

T;.;T

Sift4G

Benign

0.36

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.024

MutPred

0.18

Loss of methylation at K2267 (P = 0.0684);.;.;

MPC

0.26

ClinPred

0.018

GERP RS

4.6

Varity_R

0.078

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over