Variant chr15-62675276-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015059.3(TLN2):c.912C>T(p.Leu304Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,614,226 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

TLN2
NM_015059.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.52

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:

LOC105370855 (HGNC:):

LOC105370855 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 15-62675276-C-T is Benign according to our data. Variant chr15-62675276-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645406.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.52 with no splicing effect.

BS2

High AC in GnomAd4 at 69 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLN2	NM_015059.3 link	c.912C>T	p.Leu304Leu	synonymous_variant	11/59	ENST00000636159.2	NP_055874.2	Q9Y4G6
TLN2	NM_001394547.1 link	c.912C>T	p.Leu304Leu	synonymous_variant	10/58		NP_001381476.1
LOC105370855	XR_007064672.1 link	n.461-6204G>A		intron_variant
LOC105370855	XR_007064673.1 link	n.530-6204G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2 link	c.912C>T	p.Leu304Leu	synonymous_variant	11/59	5	NM_015059.3	ENSP00000490662.2		Q9Y4G6A0A1B0GVU7
TLN2	ENST00000561311.5 link	c.912C>T	p.Leu304Leu	synonymous_variant	10/58	5		ENSP00000453508.1		Q9Y4G6

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152216

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000247

AC:

AN:

251468

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000970

Gnomad NFE exome

AF:

0.000325

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000268

AC:

392

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000453

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000640

Hom.:

Bravo

AF:

0.000208

EpiCase

AF:

0.000545

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

TLN2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.3

DANN

Benign

0.62

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