15-62670095-C-T

Variant names:

• chr15-62670095-C-T
• rs1574119
• NM_015059.3:c.789-3732C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015059.3(TLN2):​c.789-3732C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,998 control chromosomes in the GnomAD database, including 7,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7403 hom., cov: 32)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• camptodactyly of fingers

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

LOC105370855 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLN2	NM_015059.3	MANE Select	c.789-3732C>T		intron	N/A	NP_055874.2	Q9Y4G6
	TLN2	NM_001394547.1		c.789-3732C>T		intron	N/A	NP_001381476.1	Q9Y4G6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLN2	ENST00000636159.2	TSL:5 MANE Select	c.789-3732C>T		intron	N/A	ENSP00000490662.2	Q9Y4G6
	TLN2	ENST00000561311.5	TSL:5	c.789-3732C>T		intron	N/A	ENSP00000453508.1	Q9Y4G6
	TLN2	ENST00000895916.1		c.789-3732C>T		intron	N/A	ENSP00000565975.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45844 AN: 151878 Hom.: 7394 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.282

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45879 AN: 151998 Hom.: 7403 Cov.: 32 AF XY: 0.304 AC XY: 22586 AN XY: 74294

African (AFR) AF: 0.215 AC: 8906 AN: 41458

American (AMR) AF: 0.354 AC: 5414 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3468

East Asian (EAS) AF: 0.645 AC: 3326 AN: 5158

South Asian (SAS) AF: 0.292 AC: 1404 AN: 4808

European-Finnish (FIN) AF: 0.322 AC: 3401 AN: 10562

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21735 AN: 67942

Other (OTH) AF: 0.284 AC: 601 AN: 2114

Alfa AF: 0.278 Hom.: 3242

Bravo AF: 0.305

Asia WGS AF: 0.437 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.38
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1574119; hg19: chr15-62962294;